Antimetastatic efficacy of silibinin: Molecular mechanisms and therapeutic potential against cancer

Cancer and Metastasis Reviews

Volumn 29, Issue 3, 2010, Pages 447-463

  Deep, Gagan ^a,b   Agarwal, Rajesh ^a,b  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF COLORADO CANCER CENTER   (United States)

Author keywords

EMT; Metastasis; Proteases; Silibinin; Tumor microenvironment

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE; PROTEINASE; SILIBININ;

ANTINEOPLASTIC ACTIVITY; BLADDER CANCER; BREAST CANCER; CANCER SURVIVAL; CARCINOGENESIS; COLON CANCER; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG METABOLISM; DRUG TARGETING; GLIOBLASTOMA; HUMAN; KIDNEY CANCER; LARYNX CANCER; LEUKEMIA; LIVER CANCER; LUNG CANCER; LUNG METASTASIS; METASTASIS; MOUTH CANCER; NONHUMAN; OSTEOSARCOMA; OVARY CANCER; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; SILYBUM MARIANUM; SKIN CANCER; STOMACH CANCER; UTERINE CERVIX CANCER;

ANIMALS; ANTIOXIDANTS; HUMANS; MILK THISTLE; NEOPLASM METASTASIS; NEOPLASMS; SIGNAL TRANSDUCTION; SILYMARIN;

EID: 77957598340     PISSN: 01677659     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10555-010-9237-0     Document Type: Review

References (201)

1. A Jemal R Siegel E Ward Y Hao J Xu MJ Thun 2009 Cancer statistics, 2009 CA: A Cancer Journal for Clinicians 59 4 225 249
2. LA Kingsley PG Fournier JM Chirgwin TA Guise 2007 Molecular biology of bone metastasis Molecular Cancer Therapeutics 6 10 2609 2617 1:CAS:528:DC%2BD2sXhtFKltbnE 17938257
3. K Tantivejkul LM Kalikin KJ Pienta 2004 Dynamic process of prostate cancer metastasis to bone Journal of Cellular Biochemistry 91 4 706 717 1:CAS:528:DC%2BD2cXitlGis7c%3D 14991762
4. BA Hadaschik ME Gleave 2007 Therapeutic options for hormone-refractory prostate cancer in 2007 Urologic Oncology 25 5 413 419 1:CAS:528: DC%2BD2sXhtVWhtr3N 17826663
5. P Mehlen A Puisieux 2006 Metastasis: A question of life or death Nature Reviews. Cancer 6 6 449 458 10.1038/nrc1886 1:CAS:528:DC%2BD28XkvVyltrY%3D 16723991
6. DX Nguyen J Massague 2007 Genetic determinants of cancer metastasis Nature Reviews. Genetics 8 5 341 352 10.1038/nrg2101 1:CAS:528: DC%2BD2sXktlSltLc%3D 17440531 (Pubitemid 46625811)
7. J Monteiro R Fodde 2010 Cancer stemness and metastasis: Therapeutic consequences and perspectives European Journal of Cancer 46 7 1198 1203 10.1016/j.ejca.2010.02.030/S0959-8049(10)00157-7 1:CAS:528:DC%2BC3cXkvFKqtrw%3D 20303259
8. K Polyak RA Weinberg 2009 Transitions between epithelial and mesenchymal states: Acquisition of malignant and stem cell traits Nature Reviews. Cancer 9 4 265 273 1:CAS:528:DC%2BD1MXis1Chtb0%3D 19262571
9. JA Joyce JW Pollard 2009 Microenvironmental regulation of metastasis Nature Reviews. Cancer 9 4 239 252 10.1038/nrc2618 1:CAS:528: DC%2BD1MXivFCjsLg%3D 19279573
10. J Yang RA Weinberg 2008 Epithelial-mesenchymal transition: At the crossroads of development and tumor metastasis Developmental Cell 14 6 818 829 10.1016/j.devcel.2008.05.009/S1534-5807(08)00209-8 1:CAS:528: DC%2BD1cXnsVCrs7g%3D 18539112
11. GP Gupta AJ Minn Y Kang PM Siegel I Serganova C Cordon-Cardo, et al. 2005 Identifying site-specific metastasis genes and functions Cold Spring Harbor Symposia on Quantitative Biology 70 149 158 10.1101/sqb.2005.70.018 1:CAS:528:DC%2BD28XoslChur0%3D 16869748 (Pubitemid 44124866)
12. NW Clarke CA Hart MD Brown 2009 Molecular mechanisms of metastasis in prostate cancer Asian Journal of Andrology 11 1 57 67 10.1038/aja.2008.29 1:CAS:528:DC%2BD1MXnvFCru7k%3D 19050684
13. JT Buijs G van der Pluijm 2009 Osteotropic cancers: From primary tumor to bone Cancer Letters 273 2 177 193 10.1016/j.canlet.2008.05.044/S0304-3835(08) 00450-3 1:CAS:528:DC%2BD1cXhsV2gtbrP 18632203
14. M Guarino B Rubino G Ballabio 2007 The role of epithelial-mesenchymal transition in cancer pathology Pathology 39 3 305 318 1:CAS:528: DC%2BD2sXmt1ant7o%3D 17558857
15. JJ Christiansen AK Rajasekaran 2006 Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis Cancer Research 66 17 8319 8326 1:CAS:528:DC%2BD28XovF2jtb8%3D 16951136
16. B Nieswandt M Hafner B Echtenacher DN Mannel 1999 Lysis of tumor cells by natural killer cells in mice is impeded by platelets Cancer Research 59 6 1295 1300 1:CAS:528:DyaK1MXhvFehtbo%3D 10096562
17. JS Palumbo KE Talmage JV Massari CM La Jeunesse MJ Flick KW Kombrinck, et al. 2007 Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and -independent mechanisms Blood 110 1 133 141 10.1182/blood-2007-01-065995 1:CAS:528:DC%2BD2sXnsVaisL8%3D 17371949 (Pubitemid 47026828)
18. S Karpatkin E Pearlstein PL Salk G Yogeeswaran 1981 Role of platelets in tumor cell metastases Annals of the New York Academy of Sciences 370 101 118 1:CAS:528:DyaL3MXkvFGit7w%3D 6943955 (Pubitemid 11049623)
19. IJ Fidler 2003 The pathogenesis of cancer metastasis: The 'seed and soil' hypothesis revisited Nature Reviews. Cancer 3 6 453 458 10.1038/nrc1098 1:CAS:528:DC%2BD3sXktFOnsbg%3D 12778135 (Pubitemid 37328849)
20. L Weiss 2000 Metastasis of cancer: A conceptual history from antiquity to the 1990s Cancer and Metastasis Reviews 19 3-4, I-XI 193 383
21. EV Sugarbaker 1979 Cancer metastasis: A product of tumor-host interactions Current Problems in Cancer 3 7 1 59 1:STN:280:DyaE1M7kslynsg%3D%3D 371913
22. OV Batson 1940 The function of the vertebral veins and their role in the spread of metastases Annals of Surgery 112 1 138 149 1:STN:280: DC%2BD2srkt1Krug%3D%3D 17857618
23. DR Coman RP de Long 1951 The role of the vertebral venous system in the metastasis of cancer to the spinal column; experiments with tumor-cell suspensions in rats and rabbits Cancer 4 3 610 618 1:STN:280: DyaG3M%2FmvFWltw%3D%3D 14839615
24. GJ Klarmann EM Hurt LA Mathews X Zhang MA Duhagon T Mistree, et al. 2009 Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature Clinical & Experimental Metastasis 26 5 433 446 1:CAS:528:DC%2BD1MXmtVKgsLY%3D
25. EM Hurt BT Kawasaki GJ Klarmann SB Thomas WL Farrar 2008 CD44+ CD24(-) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis British Journal of Cancer 98 4 756 765 1:CAS:528:DC%2BD1cXitVGhtbk%3D 18268494
26. Y Kang PM Siegel W Shu M Drobnjak SM Kakonen C Cordon-Cardo, et al. 2003 A multigenic program mediating breast cancer metastasis to bone Cancer Cell 3 6 537 549 S1535610803001326 1:CAS:528:DC%2BD3sXltlSmsL4%3D 12842083
27. RR Langley IJ Fidler 2007 Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis Endocrine Reviews 28 3 297 321 10.1210/er.2006-0027 1:CAS:528:DC%2BD2sXmsVGlu74%3D 17409287 (Pubitemid 46984829)
28. RN Kaplan RD Riba S Zacharoulis AH Bramley L Vincent C Costa, et al. 2005 VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche Nature 438 7069 820 827 10.1038/nature04186 1:CAS:528:DC%2BD2MXht1ynsrnL 16341007 (Pubitemid 41753060)
29. JT Erler KL Bennewith TR Cox G Lang D Bird A Koong, et al. 2009 Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche Cancer Cell 15 1 35 44 10.1016/j.ccr.2008.11.012/S1535-6108(08)00378-4 1:CAS:528:DC%2BD1MXptVGqug%3D%3D 19111879
30. R Demicheli MW Retsky WJ Hrushesky M Baum 2007 Tumor dormancy and surgery-driven interruption of dormancy in breast cancer: Learning from failures Nature Clinical Practice. Oncology 4 12 699 710 10.1038/ncponc0999 18037874 (Pubitemid 350187005)
31. R Demicheli MW Retsky DE Swartzendruber G Bonadonna 1997 Proposal for a new model of breast cancer metastatic development Annals of Oncology 8 11 1075 1080 1:STN:280:DyaK1c%2FoslOjtA%3D%3D 9426326
32. DA Lawson Y Zong S Memarzadeh L Xin J Huang ON Witte 2010 Basal epithelial stem cells are efficient targets for prostate cancer initiation Proceedings of the National Academy of Sciences of the United States of America 107 6 2610 2615 0913873107 1:CAS:528:DC%2BC3cXit1aksb8%3D 20133806
33. JE Visvader GJ Lindeman 2008 Cancer stem cells in solid tumours: Accumulating evidence and unresolved questions Nature Reviews. Cancer 8 10 755 768 10.1038/nrc2499 1:CAS:528:DC%2BD1cXhtFCrtb3K 18784658
34. EM Hurt WL Farrar 2008 Cancer stem cells: The seeds of metastasis? Molecular Interventions 8 3 140 142 18693193
35. AF Chambers AC Groom IC MacDonald 2002 Dissemination and growth of cancer cells in metastatic sites Nature Reviews. Cancer 2 8 563 572 1:CAS:528:DC%2BD38XlslGqsLw%3D 12154349
36. 125I-5-iodo-2′-deoxyuridine Journal of the National Cancer Institute 45 4 773 782 1:CAS:528: DyaE3cXlt1yqsrg%3D 5513503
37. SA Mani W Guo MJ Liao EN Eaton A Ayyanan AY Zhou, et al. 2008 The epithelial-mesenchymal transition generates cells with properties of stem cells Cell 133 4 704 715 10.1016/j.cell.2008.03.027/S0092-8674(08)00444-3 1:CAS:528:DC%2BD1cXmsVOru7w%3D 18485877
38. P Elvin AP Garner 2005 Tumour invasion and metastasis: Challenges facing drug discovery Current Opinion in Pharmacology 5 4 374 381 10.1016/j.coph.2005. 02.008/S1471-4892(05)00074-3 1:CAS:528:DC%2BD2MXlvFKlsLs%3D 15955738
39. NP Nguyen M Bishop TJ Borok J Welsh R Hamilton D Cohen, et al. 2010 Pattern of failure following chemoradiation for locally advanced non-small cell lung cancer: Potential role for stereotactic body radiotherapy Anticancer Research 30 3 953 961 30/3/953 1:CAS:528:DC%2BC3cXlslelu78%3D 20393019
40. MI Gimbel PB Paty 2004 A current perspective on local excision of rectal cancer Clinical Colorectal Cancer 4 1 26 35 15207017 discussion 36-27
41. CM Wilson S Tobin RC Young 2004 The exploding worldwide cancer burden: The impact of cancer on women International Journal of Gynecological Cancer 14 1 1 11 14178 1:STN:280:DC%2BD2c%2FmtleqsA%3D%3D 14764024
42. I Magrath J Litvak 1993 Cancer in developing countries: Opportunity and challenge Journal of the National Cancer Institute 85 11 862 874 1:STN:280:DyaK3s3mtVOhsw%3D%3D 8492315
43. BB Aggarwal ME Van Kuiken LH Iyer KB Harikumar B Sung 2009 Molecular targets of nutraceuticals derived from dietary spices: Potential role in suppression of inflammation and tumorigenesis Experimental Biology and Medicine (Maywood) 234 8 825 849 10.3181/0902-MR-78 1:CAS:528:DC%2BD1MXpt1WksLw%3D
44. G Trottier PJ Bostrom N Lawrentschuk NE Fleshner 2010 Nutraceuticals and prostate cancer prevention: A current review Nature Reviews Urology 7 1 21 30 10.1038/nrurol.2009.234 1:CAS:528:DC%2BC3cXjtlaruw%3D%3D 19997071
45. R Agarwal G Deep 2008 Kava, a tonic for relieving the irrational development of natural preventive agents Cancer Prevention Research (Philadelphia, PA) 1 6 409 412 1:CAS:528:DC%2BC3cXptVyru7s%3D
46. T Dennis M Fanous S Mousa 2009 Natural products for chemopreventive and adjunctive therapy in oncologic disease Nutrition and Cancer 61 5 587 597 10.1080/01635580902825530/914447574 1:CAS:528:DC%2BD1MXht12gsr%2FM 19838932
47. BB Aggarwal AB Kunnumakkara KB Harikumar ST Tharakan B Sung P Anand 2008 Potential of spice-derived phytochemicals for cancer prevention Planta Medica 74 13 1560 1569 1:CAS:528:DC%2BD1cXhtl2hsb3P 18612945
48. R Agarwal C Agarwal H Ichikawa RP Singh BB Aggarwal 2006 Anticancer potential of silymarin: From bench to bed side Anticancer Research 26 6B 4457 4498 1:CAS:528:DC%2BD2sXpslGjtQ%3D%3D 17201169
49. P Anand C Sundaram S Jhurani AB Kunnumakkara BB Aggarwal 2008 Curcumin and cancer: An "Old-age" disease with an "Age-old" solution Cancer Letters 267 1 133 164 10.1016/j.canlet.2008.03.025/S0304-3835(08)00231-0 1:CAS:528:DC%2BD1cXotlCgtbs%3D 18462866
50. A Basu V Imrhan 2007 Tomatoes versus lycopene in oxidative stress and carcinogenesis: Conclusions from clinical trials European Journal of Clinical Nutrition 61 3 295 303 10.1038/sj.ejcn.1602510 1:CAS:528:DC%2BD2sXit12qtrY%3D 16929242 (Pubitemid 46358768)
51. VD Longo L Fontana 2010 Calorie restriction and cancer prevention: Metabolic and molecular mechanisms Trends in Pharmacological Sciences 31 2 89 98 10.1016/j.tips.2009.11.004/S0165-6147(09)00202-8 1:CAS:528:DC%2BC3cXhtlejsbc%3D 20097433
52. DL Bemis AE Katz R Buttyan 2006 Clinical trials of natural products as chemopreventive agents for prostate cancer Expert Opinion on Investigational Drugs 15 10 1191 1200 1:CAS:528:DC%2BD28XpvVeisLc%3D 16989596
53. AF Chambers 2009 Influence of diet on metastasis and tumor dormancy Clinical & Experimental Metastasis 26 1 61 66 10.1007/s10585-008-9164-4 1:CAS:528:DC%2BD1MXhtVCgt78%3D
54. CH Hsu AL Cheng 2007 Clinical studies with curcumin Advances in Experimental Medicine and Biology 595 471 480 10.1007/978-0-387-46401-521 17569225
55. TW Flaig M Glode D Gustafson A van Bokhoven Y Tao S Wilson, et al. 2010 A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer Prostate 70 8 848 855 10.1002/pros.21118 1:CAS:528:DC%2BC3cXnvFGqs7o%3D 20127732
56. TW Flaig DL Gustafson LJ Su JA Zirrolli F Crighton GS Harrison, et al. 2007 A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients Investigational New Drugs 25 2 139 146 1:CAS:528:DC%2BD28XhtlCksbnN 17077998
57. SC Pradhan C Girish 2006 Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine The Indian Journal of Medical Research 124 5 491 504 1:CAS:528:DC%2BD2sXjtlKjtLs%3D 17213517
58. F Rainone 2005 Milk thistle American Family Physician 72 7 1285 1288 16225032
59. J Post-White EJ Ladas KM Kelly 2007 Advances in the use of milk thistle (Silybum marianum) Integrative Cancer Therapies 6 2 104 109 10.1177/ 1534735407301632/6/2/104 1:CAS:528:DC%2BD2sXnt1Glt7w%3D 17548789
60. PR Davis-Searles Y Nakanishi NC Kim TN Graf NH Oberlies MC Wani, et al. 2005 Milk thistle and prostate cancer: Differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells Cancer Research 65 10 4448 4457 1:CAS:528: DC%2BD2MXktlSmtbw%3D 15899838
61. Z Wen TE Dumas SJ Schrieber RL Hawke MW Fried PC Smith 2008 Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract Drug Metabolism and Disposition 36 1 65 72 1:CAS:528:DC%2BD1cXmtFGksg%3D%3D 17913795
62. R Venkataramanan B Komoroski S Strom 2006 In vitro and in vivo assessment of herb drug interactions Life Sciences 78 18 2105 2115 10.1016/j.lfs.2005.12. 021/S0024-3205(05)01249-X 1:CAS:528:DC%2BD28XisF2qsb8%3D 16427092
63. K Flora M Hahn H Rosen K Benner 1998 Milk thistle (Silybum marianum) for the therapy of liver disease The American Journal of Gastroenterology 93 2 139 143 1:CAS:528:DyaK1cXmt1Grsrk%3D 9468229
64. Silybin-phosphatidylcholine complex. Monograph. Alternative Medicine Review, 14(4), 385-390 (2009).
65. PM Kidd 2009 Bioavailability and activity of phytosome complexes from botanical polyphenols: The silymarin, curcumin, green tea, and grape seed extracts Alternative Medicine Review 14 3 226 246 19803548
66. X Yanyu S Yunmei C Zhipeng P Qineng 2006 The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats International Journal of Pharmaceutics 307 1 77 82 16300915
67. Y Wang D Zhang Z Liu G Liu C Duan L Jia, et al. 2010 In vitro and in vivo evaluation of silybin nanosuspensions for oral and intravenous delivery Nanotechnology 21 15 155104
68. P Kidd K Head 2005 A review of the bioavailability and clinical efficacy of milk thistle phytosome: A silybin-phosphatidylcholine complex (Siliphos) Alternative Medicine Review 10 3 193 203 16164374
69. C Hoh D Boocock T Marczylo R Singh DP Berry AR Dennison, et al. 2006 Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: Silibinin levels in plasma, colorectum, and liver and their pharmacodynamic consequences Clinical Cancer Research 12 9 2944 2950 1:CAS:528:DC%2BD28Xltlamurs%3D 16675592
70. G Deep RP Singh C Agarwal DJ Kroll R Agarwal 2006 Silymarin and silibinin cause G1 and G2-M cell cycle arrest via distinct circuitries in human prostate cancer PC3 cells: A comparison of flavanone silibinin with flavanolignan mixture silymarin Oncogene 25 7 1053 1069 1:CAS:528:DC%2BD28XhsVehsro%3D 16205633
71. S Mateen A Tyagi C Agarwal RP Singh R Agarwal 2010 Silibinin inhibits human nonsmall cell lung cancer cell growth through cell-cycle arrest by modulating expression and function of key cell-cycle regulators Molecular Carcinogenesis 49 3 247 258 10.1002/mc.20595 1:CAS:528:DC%2BC3cXitF2ks7c%3D 19908243
72. X Zi R Agarwal 1999 Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: Implications for prostate cancer intervention Proceedings of the National Academy of Sciences of the United States of America 96 13 7490 7495 1:CAS:528:DyaK1MXltVOqsL4%3D 10377442
73. A Tyagi C Agarwal R Agarwal 2002 The cancer preventive flavonoid silibinin causes hypophosphorylation of Rb/p107 and Rb2/p130 via modulation of cell cycle regulators in human prostate carcinoma DU145 cells Cell Cycle 1 2 137 142 1:CAS:528:DC%2BD38Xnt1yitL4%3D 12429923
74. M Kaur B Velmurugan A Tyagi G Deep S Katiyar C Agarwal, et al. 2009 Silibinin suppresses growth and induces apoptotic death of human colorectal carcinoma LoVo cells in culture and tumor xenograft Molecular Cancer Therapeutics 8 8 2366 2374 1:CAS:528:DC%2BD1MXpvFCms74%3D 19638451
75. C Agarwal RP Singh S Dhanalakshmi AK Tyagi M Tecklenburg RA Sclafani, et al. 2003 Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells Oncogene 22 51 8271 8282 1:CAS:528:DC%2BD3sXovVyms7c%3D 14614451
76. L Li Y Gao L Zhang J Zeng D He Y Sun 2008 Silibinin inhibits cell growth and induces apoptosis by caspase activation, down-regulating survivin and blocking EGFR-ERK activation in renal cell carcinoma Cancer Letters 272 1 61 69 10.1016/j.canlet.2008.06.033/S0304-3835(08)00520-X 1:CAS:528: DC%2BD1cXht1Knt7%2FI 18723275
77. HJ Wang S Tashiro S Onodera T Ikejima 2008 Inhibition of insulin-like growth factor 1 receptor signaling enhanced silibinin-induced activation of death receptor and mitochondrial apoptotic pathways in human breast cancer MCF-7 cells Journal of Pharmacological Sciences 107 3 260 269 JST.JSTAGE/jphs/08054FP 1:CAS:528:DC%2BD1cXpt12mtrc%3D 18635919
78. YG Son EH Kim JY Kim SU Kim TK Kwon AR Yoon, et al. 2007 Silibinin sensitizes human glioma cells to TRAIL-mediated apoptosis via DR5 up-regulation and down-regulation of c-FLIP and survivin Cancer Research 67 17 8274 8284 1:CAS:528:DC%2BD2sXpvFKju74%3D 17804742
79. RP Singh S Dhanalakshmi C Agarwal R Agarwal 2005 Silibinin strongly inhibits growth and survival of human endothelial cells via cell cycle arrest and downregulation of survivin, Akt and NF-kappab: Implications for angioprevention and antiangiogenic therapy Oncogene 24 7 1188 1202 1:CAS:528:DC%2BD2MXhtFGqs7o%3D 15558015
80. K Raina S Rajamanickam RP Singh G Deep M Chittezhath R Agarwal 2008 Stage-specific inhibitory effects and associated mechanisms of silibinin on tumor progression and metastasis in transgenic adenocarcinoma of the mouse prostate model Cancer Research 68 16 6822 6830 1:CAS:528:DC%2BD1cXpslKmt7c%3D 18701508
81. RP Singh G Deep M Chittezhath M Kaur LD Dwyer-Nield AM Malkinson, et al. 2006 Effect of silibinin on the growth and progression of primary lung tumors in mice Journal of the National Cancer Institute 98 12 846 855 1:CAS:528:DC%2BD28Xmt1Wktr4%3D 16788158
82. RP Singh G Sharma S Dhanalakshmi C Agarwal R Agarwal 2003 Suppression of advanced human prostate tumor growth in athymic mice by silibinin feeding is associated with reduced cell proliferation, increased apoptosis, and inhibition of angiogenesis Cancer Epidemiology, Biomarkers & Prevention 12 9 933 939 1:CAS:528:DC%2BD3sXnsValt7c%3D
83. RP Singh R Agarwal 2006 Prostate cancer chemoprevention by silibinin: Bench to bedside Molecular Carcinogenesis 45 6 436 442 1:CAS:528: DC%2BD28XlvVCnsbs%3D 16637061 (Pubitemid 43865852)
84. S Rajamanickam B Velmurugan M Kaur RP Singh R Agarwal 2010 Chemoprevention of intestinal tumorigenesis in APCmin/+ mice by silibinin Cancer Research 70 6 2368 2378 10.1158/0008-5472.CAN-09-3249 1:CAS:528: DC%2BC3cXjtFygtLo%3D 20215518
85. RP Singh R Agarwal 2004 Prostate cancer prevention by silibinin Current Cancer Drug Targets 4 1 1 11
86. RP Singh K Raina G Deep D Chan R Agarwal 2009 Silibinin suppresses growth of human prostate carcinoma PC-3 orthotopic xenograft via activation of extracellular signal-regulated kinase 1/2 and inhibition of signal transducers and activators of transcription signaling Clinical Cancer Research 15 2 613 621 1:CAS:528:DC%2BD1MXlvFeqsw%3D%3D 19147767
87. L Li J Zeng Y Gao D He 2010 Targeting silibinin in the antiproliferative pathway Expert Opinion on Investigational Drugs 19 2 243 255 10.1517/13543780903533631 1:CAS:528:DC%2BC3cXlvFakuw%3D%3D 20047507
88. A Tyagi Y Sharma C Agarwal R Agarwal 2008 Silibinin impairs constitutively active TGFalpha-EGFR autocrine loop in advanced human prostate carcinoma cells Pharmaceutical Research 25 9 2143 2150 1:CAS:528: DC%2BD1cXps1ajtbY%3D 18253818
89. HJ Jung JW Park JS Lee SR Lee BC Jang SI Suh, et al. 2009 Silibinin inhibits expression of HIF-1alpha through suppression of protein translation in prostate cancer cells Biochemical and Biophysical Research Communications 390 1 71 76 10.1016/j.bbrc.2009.09.068/S0006-291X(09)01877-4 1:CAS:528: DC%2BD1MXht1yltb7L 19778521
90. RP Singh K Raina G Sharma R Agarwal 2008 Silibinin inhibits established prostate tumor growth, progression, invasion, and metastasis and suppresses tumor angiogenesis and epithelial-mesenchymal transition in transgenic adenocarcinoma of the mouse prostate model mice Clinical Cancer Research 14 23 7773 7780 10.1158/1078-0432.CCR-08-1309/14/23/7773 1:CAS:528:DC%2BD1cXhsVegtrfO 19047104
91. MJ Mokhtari N Motamed MA Shokrgozar 2008 Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line Cell Biology International 32 8 888 892 1:CAS:528:DC%2BD1cXptVWlu7w%3D 18538589
92. K Wu J Zeng L Li J Fan D Zhang Y Xue, et al. 2010 Silibinin reverses epithelial-to-mesenchymal transition in metastatic prostate cancer cells by targeting transcription factors Oncology Reports 23 6 1545 1552 1:CAS:528:DC%2BC3cXmvFyqsbk%3D 20428808
93. KJ Wu J Zeng GD Zhu LL Zhang D Zhang L Li, et al. 2009 Silibinin inhibits prostate cancer invasion, motility and migration by suppressing vimentin and MMP-2 expression Acta Pharmacologica Sinica 30 8 1162 1168 10.1038/aps.2009.94 1:CAS:528:DC%2BD1MXpsVejtrg%3D 19578386
94. Deep, G., Gangar, S. C., & Agarwal, R. (2010). Silibinin inhibits epithelial to mesenchymal transition in prostate cancer cells: Role of E-cadherin and beyond. Proceedings of the 101th AACR Annual Meeting, Washington DC, April 2010. Abstract number 5650.
95. AM Handorean K Yang EW Robbins TW Flaig KA Iczkowski 2009 Silibinin suppresses CD44 expression in prostate cancer cells American Journal of Translational Research 1 1 80 86 1:CAS:528:DC%2BD1MXhtFejs7jK 19966941
96. P Msaouel N Pissimissis A Halapas M Koutsilieris 2008 Mechanisms of bone metastasis in prostate cancer: Clinical implications Best Practice & Research. Clinical Endocrinology & Metabolism 22 2 341 355 10.1016/j.beem.2008.01.011/S1521-690X(08)00012-2 1:CAS:528:DC%2BD1cXlslygtrk%3D
97. JH Kim K Kim HM Jin I Song BU Youn J Lee, et al. 2009 Silibinin inhibits osteoclast differentiation mediated by TNF family members Molecules and Cells 10.1007/s10059-009-0123-y
98. Gangar, S. C., Deep, G., & Agarwal, R. (2010). Silibinin inhibits advanced human prostate carcinoma-induced osteoclastogenesis. Proceedings of the 101th AACR Annual Meeting, Washington DC, April 2010. Abstract number 5661.
99. M Provinciali F Papalini F Orlando S Pierpaoli A Donnini P Morazzoni, et al. 2007 Effect of the silybin-phosphatidylcholine complex (IdB 1016) on the development of mammary tumors in HER-2/neu transgenic mice Cancer Research 67 5 2022 2029 1:CAS:528:DC%2BD2sXit12qu70%3D 17332330
100. SO Lee YJ Jeong HG Im CH Kim YC Chang IS Lee 2007 Silibinin suppresses PMA-induced MMP-9 expression by blocking the AP-1 activation via MAPK signaling pathways in MCF-7 human breast carcinoma cells Biochemical and Biophysical Research Communications 354 1 165 171 1:CAS:528:DC%2BD2sXhtVClsrg%3D 17214970
101. PN Chen YS Hsieh CL Chiang HL Chiou SF Yang SC Chu 2006 Silibinin inhibits invasion of oral cancer cells by suppressing the MAPK pathway Journal of Dental Research 85 3 220 225 1:CAS:528:DC%2BD28Xis1OqsL8%3D 16498067
102. SC Chu HL Chiou PN Chen SF Yang YS Hsieh 2004 Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2 Molecular Carcinogenesis 40 3 143 149 1:CAS:528:DC%2BD2cXlvFKgsLs%3D 15224346
103. YS Hsieh SC Chu SF Yang PN Chen YC Liu KH Lu 2007 Silibinin suppresses human osteosarcoma MG-63 cell invasion by inhibiting the ERK-dependent c-Jun/AP-1 induction of MMP-2 Carcinogenesis 28 5 977 987 10.1093/carcin/bgl221 1:CAS:528:DC%2BD2sXlvFGlsL0%3D 17116726 (Pubitemid 47072181)
104. S Baranwal SK Alahari 2009 Molecular mechanisms controlling E-cadherin expression in breast cancer Biochemical and Biophysical Research Communications 384 1 6 11 10.1016/j.bbrc.2009.04.051/S0006-291X(09)00688-3 1:CAS:528: DC%2BD1MXmtFShtro%3D 19379710
105. YG Jiang Y Luo DL He X Li LL Zhang T Peng, et al. 2007 Role of Wnt/beta-catenin signaling pathway in epithelial-mesenchymal transition of human prostate cancer induced by hypoxia-inducible factor-1alpha International Journal of Urology 14 11 1034 1039 10.1111/j.1442-2042.2007.01866.x/IJU1866 1:CAS:528:DC%2BD1cXjs1Wmuw%3D%3D 17956532
106. R Roy J Yang MA Moses 2009 Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer Journal of Clinical Oncology 27 31 5287 5297 10.1200/JCO.2009.23.5556 1:CAS:528:DC%2BD1MXhsFahsLnP 19738110
107. P Vihinen VM Kahari 2002 Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets International Journal of Cancer 99 2 157 166 10.1002/ijc.10329 1:CAS:528:DC%2BD38XivFyrsr4%3D (Pubitemid 34309470)
108. T Itoh M Tanioka H Matsuda H Nishimoto T Yoshioka R Suzuki, et al. 1999 Experimental metastasis is suppressed in MMP-9-deficient mice Clinical & Experimental Metastasis 17 2 177 181 1:CAS:528:DyaK1MXltVKjt7k%3D
109. T Itoh M Tanioka H Yoshida T Yoshioka H Nishimoto S Itohara 1998 Reduced angiogenesis and tumor progression in gelatinase a-deficient mice Cancer Research 58 5 1048 1051 1:CAS:528:DyaK1cXhsFersLo%3D 9500469
110. S Garbisa G Scagliotti L Masiero C Di Francesco C Caenazzo M Onisto, et al. 1992 Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy Cancer Research 52 16 4548 4549 1:CAS:528:DyaK38Xls1yltL0%3D 1322794
111. V Noe B Fingleton K Jacobs HC Crawford S Vermeulen W Steelant, et al. 2001 Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1 Journal of Cell Science 114 Pt 1 111 118 1:CAS:528: DC%2BD3MXhtVSgsL8%3D 11112695
112. X Li JF Wu 2010 Recent developments in patent anti-cancer agents targeting the matrix metalloproteinases (MMPs) Recent Patents on Anticancer Drug Discovery 5 2 109 141 E-Pub PRA-ABS-Li-18 1:CAS:528:DC%2BC3cXmsVamt7c%3D
113. DE Gomez DF Alonso H Yoshiji UP Thorgeirsson 1997 Tissue inhibitors of metalloproteinases: Structure, regulation and biological functions European Journal of Cell Biology 74 2 111 122 1:CAS:528:DyaK2sXmslSqsLg%3D 9352216
114. PN Chen YS Hsieh HL Chiou SC Chu 2005 Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways Chemico-Biological Interactions 156 2-3 141 150 1:CAS:528:DC%2BD2MXhtVymsLrM 16169542
115. M Momeny MR Khorramizadeh SH Ghaffari M Yousefi MS Yekaninejad R Esmaeili, et al. 2008 Effects of silibinin on cell growth and invasive properties of a human hepatocellular carcinoma cell line, HepG-2, through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation European Journal of Pharmacology 591 1-3 13 20 10.1016/j.ejphar.2008.06.011/S0014- 2999(08)00625-0 1:CAS:528:DC%2BD1cXps12lsrs%3D 18599034
116. M Momeny M Malehmir M Zakidizaji R Ghasemi H Ghadimi MA Shokrgozar, et al. 2010 Silibinin inhibits invasive properties of human glioblastoma U87MG cells through suppression of cathepsin B and nuclear factor kappa b-mediated induction of matrix metalloproteinase 9 Anticancer Drugs 21 3 252 260 1:CAS:528:DC%2BC3cXhsVWitLc%3D 20166242
117. JS Rao 2003 Molecular mechanisms of glioma invasiveness: The role of proteases Nature Reviews. Cancer 3 7 489 501 10.1038/nrc1121 1:CAS:528:DC%2BD3sXltVSqtr8%3D 12835669
118. S Mohanam RE Sawaya M Yamamoto JM Bruner GL Nicholson JS Rao 1994 Proteolysis and invasiveness of brain tumors: Role of urokinase-type plasminogen activator receptor Journal of Neurooncology 22 2 153 160 1:STN:280: DyaK2M3msVWqtQ%3D%3D
119. S Mohanam CL Gladson CN Rao JS Rao 1999 Biological significance of the expression of urokinase-type plasminogen activator receptors (uPARs) in brain tumors Frontiers in Bioscience 4 D178 D187 1:CAS:528:DyaK1MXitFKjtrk%3D 9989951
120. C Huang K Jacobson MD Schaller 2004 MAP kinases and cell migration Journal of Cell Science 117 Pt 20 4619 4628 10.1242/jcs.01481/117/20/4619 1:CAS:528:DC%2BD2cXptVygtb8%3D 15371522
121. C Huang K Jacobson MD Schaller 2004 A role for JNK-paxillin signaling in cell migration Cell Cycle 3 1 4 6 601 1:CAS:528:DC%2BD2cXhtlWgt7c%3D 14657652
122. WS Wu JR Wu CT Hu 2008 Signal cross talks for sustained MAPK activation and cell migration: The potential role of reactive oxygen species Cancer and Metastasis Reviews 27 2 303 314 10.1007/s10555-008-9112-4 1:CAS:528: DC%2BD1cXlt1Ckuro%3D 18299806
123. S Silletti M Yebra B Perez V Cirulli M McMahon AM Montgomery 2004 Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to l1 cell adhesion molecule-dependent motility and invasion The Journal of Biological Chemistry 279 28 28880 28888 10.1074/jbc.M404075200 1:CAS:528:DC%2BD2cXlsVCnsbs%3D 15128735 (Pubitemid 38915755)
124. RP Singh S Dhanalakshmi S Mohan C Agarwal R Agarwal 2006 Silibinin inhibits UVB- and epidermal growth factor-induced mitogenic and cell survival signaling involving activator protein-1 and nuclear factor-kappab in mouse epidermal JB6 cells Molecular Cancer Therapeutics 5 5 1145 1153 1:CAS:528:DC%2BD28XltVWntbg%3D 16731746
125. M Gu S Dhanalakshmi S Mohan RP Singh R Agarwal 2005 Silibinin inhibits ultraviolet B radiation-induced mitogenic and survival signaling, and associated biological responses in SKH-1 mouse skin Carcinogenesis 26 8 1404 1413 1:CAS:528:DC%2BD2MXmsV2isbc%3D 15831527
126. G Mallikarjuna S Dhanalakshmi RP Singh C Agarwal R Agarwal 2004 Silibinin protects against photocarcinogenesis via modulation of cell cycle regulators, mitogen-activated protein kinases, and Akt signaling Cancer Research 64 17 6349 6356 1:CAS:528:DC%2BD2cXntFClt7c%3D 15342425
127. A Tyagi RP Singh K Ramasamy K Raina EF Redente LD Dwyer-Nield, et al. 2009 Growth inhibition and regression of lung tumors by silibinin: Modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-kappab and signal transducers and activators of transcription 3 Cancer Prevention Research (Philadelphia, PA) 2 1 74 83 10.1158/1940-6207.CAPR-08-0095/2/1/74 1:CAS:528:DC%2BC3cXptFOisrw%3D
128. RP Singh M Gu R Agarwal 2008 Silibinin inhibits colorectal cancer growth by inhibiting tumor cell proliferation and angiogenesis Cancer Research 68 6 2043 2050 1:CAS:528:DC%2BD1cXjtFOht7o%3D 18339887
129. RP Singh G Deep MJ Blouin MN Pollak R Agarwal 2007 Silibinin suppresses in vivo growth of human prostate carcinoma PC-3 tumor xenograft Carcinogenesis 28 12 2567 2574 1:CAS:528:DC%2BD2sXhsVWgs77L 17916909
130. M Gu RP Singh S Dhanalakshmi C Agarwal R Agarwal 2007 Silibinin inhibits inflammatory and angiogenic attributes in photocarcinogenesis in SKH-1 hairless mice Cancer Research 67 7 3483 3491 1:CAS:528:DC%2BD2sXksVGktr0%3D 17409458
131. M Chittezhath G Deep RP Singh C Agarwal R Agarwal 2008 Silibinin inhibits cytokine-induced signaling cascades and down-regulates inducible nitric oxide synthase in human lung carcinoma A549 cells Molecular Cancer Therapeutics 7 7 1817 1826 1:CAS:528:DC%2BD1cXoslCgtLg%3D 18644994
132. P Thelen W Wuttke H Jarry M Grzmil RH Ringert 2004 Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells Journal d'Urologie 171 5 1934 1938 1:CAS:528: DC%2BD2cXktVOltbY%3D
133. Y Sharma C Agarwal AK Singh R Agarwal 2001 Inhibitory effect of silibinin on ligand binding to erbB1 and associated mitogenic signaling, growth, and DNA synthesis in advanced human prostate carcinoma cells Molecular Carcinogenesis 30 4 224 236 1:CAS:528:DC%2BD3MXjsVajtb8%3D 11346885
134. G Deep NH Oberlies DJ Kroll R Agarwal 2008 Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells International Journal of Cancer 123 1 41 50 1:CAS:528:DC%2BD1cXmtlant78%3D
135. TW Flaig LJ Su G Harrison R Agarwal LM Glode 2007 Silibinin synergizes with mitoxantrone to inhibit cell growth and induce apoptosis in human prostate cancer cells International Journal of Cancer 120 9 2028 2033 1:CAS:528:DC%2BD2sXjsVCqtr8%3D (Pubitemid 46418384)
136. S Dhanalakshmi RP Singh C Agarwal R Agarwal 2002 Silibinin inhibits constitutive and TNFalpha-induced activation of NF-kappab and sensitizes human prostate carcinoma DU145 cells to TNFalpha-induced apoptosis Oncogene 21 11 1759 1767 1:CAS:528:DC%2BD38XisVShs74%3D 11896607 (Pubitemid 34259039)
137. AK Tyagi RP Singh C Agarwal DC Chan R Agarwal 2002 Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth inhibition, G2-M arrest, and apoptosis Clinical Cancer Research 8 11 3512 3519 1:CAS:528:DC%2BD38XpsVCgtLk%3D 12429642
138. C Agarwal A Tyagi M Kaur R Agarwal 2007 Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma DU145 cells Carcinogenesis 28 7 1463 1470 1:CAS:528:DC%2BD2sXos12itr8%3D 17341659
139. S Dhanalakshmi P Agarwal LM Glode R Agarwal 2003 Silibinin sensitizes human prostate carcinoma DU145 cells to cisplatin- and carboplatin-induced growth inhibition and apoptotic death International Journal of Cancer 106 5 699 705 1:CAS:528:DC%2BD3sXms1Squ7g%3D
140. S Roy M Kaur C Agarwal M Tecklenburg RA Sclafani R Agarwal 2007 p21 and p27 induction by silibinin is essential for its cell cycle arrest effect in prostate carcinoma cells Molecular Cancer Therapeutics 6 10 2696 2707 1:CAS:528:DC%2BD2sXhtFKltbbL 17938263
141. A Tyagi C Agarwal R Agarwal 2002 Inhibition of retinoblastoma protein (Rb) phosphorylation at serine sites and an increase in Rb-E2F complex formation by silibinin in androgen-dependent human prostate carcinoma LNCaP cells: Role in prostate cancer prevention Molecular Cancer Therapeutics 1 7 525 532 1:CAS:528:DC%2BD38XktlSksbk%3D 12479270
142. X Zi J Zhang R Agarwal M Pollak 2000 Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells Cancer Research 60 20 5617 5620 1:CAS:528:DC%2BD3cXnvVSnsLo%3D 11059749
143. P Thelen H Jarry RH Ringert W Wuttke 2004 Silibinin down-regulates prostate epithelium-derived Ets transcription factor in LNCaP prostate cancer cells Planta Medica 70 5 397 400 1:CAS:528:DC%2BD2cXktlOkur4%3D 15124082
144. A Tyagi N Bhatia MS Condon MC Bosland C Agarwal R Agarwal 2002 Antiproliferative and apoptotic effects of silibinin in rat prostate cancer cells The Prostate 53 3 211 217 10.1002/pros.10146 1:CAS:528: DC%2BD38XptVGlsbk%3D 12386921 (Pubitemid 35266181)
145. W Zhu JS Zhang CY Young 2001 Silymarin inhibits function of the androgen receptor by reducing nuclear localization of the receptor in the human prostate cancer cell line LNCaP Carcinogenesis 22 9 1399 1403 1:CAS:528: DC%2BD3MXmvVymtL8%3D 11532861
146. N Bhatia J Zhao DM Wolf R Agarwal 1999 Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: Comparison with silymarin Cancer Letters 147 1-2 77 84 1:CAS:528: DyaK1MXns1ags78%3D 10660092
147. G Deep K Raina RP Singh NH Oberlies DJ Kroll R Agarwal 2008 Isosilibinin inhibits advanced human prostate cancer growth in athymic nude mice: Comparison with silymarin and silibinin International Journal of Cancer 123 12 2750 2758 1:CAS:528:DC%2BD1cXhsVKgtrbE
148. RP Singh S Dhanalakshmi AK Tyagi DC Chan C Agarwal R Agarwal 2002 Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels Cancer Research 62 11 3063 3069 1:CAS:528:DC%2BD38XksVyqsr4%3D 12036915
149. K Raina NJ Serkova R Agarwal 2009 Silibinin feeding alters the metabolic profile in TRAMP prostatic tumors: 1H-NMRS-based metabolomics study Cancer Research 69 9 3731 3735 10.1158/0008-5472.CAN-09-0096 1:CAS:528: DC%2BD1MXltFOksrk%3D 19366793
150. RD Verschoyle P Greaves K Patel DA Marsden K Brown WP Steward, et al. 2008 Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: Relationship with silibinin levels European Journal of Cancer 44 6 898 906 1:CAS:528: DC%2BD1cXks1Gmsrc%3D 18343654
151. S Dhanalakshmi C Agarwal RP Singh R Agarwal 2005 Silibinin up-regulates DNA-protein kinase-dependent p53 activation to enhance UVB-induced apoptosis in mouse epithelial JB6 cells The Journal of Biological Chemistry 280 21 20375 20383 1:CAS:528:DC%2BD2MXktlCmu74%3D 15792956
152. S Dhanalakshmi GU Mallikarjuna RP Singh R Agarwal 2004 Dual efficacy of silibinin in protecting or enhancing ultraviolet B radiation-caused apoptosis in HaCaT human immortalized keratinocytes Carcinogenesis 25 1 99 106 1:CAS:528:DC%2BD2cXnslWn 14555614
153. S Mohan S Dhanalakshmi GU Mallikarjuna RP Singh R Agarwal 2004 Silibinin modulates UVB-induced apoptosis via mitochondrial proteins, caspases activation, and mitogen-activated protein kinase signaling in human epidermoid carcinoma A431 cells Biochemical and Biophysical Research Communications 320 1 183 189 1:CAS:528:DC%2BD2cXltVKgsbg%3D 15207719
154. N Bhatia C Agarwal R Agarwal 2001 Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells Nutrition and Cancer 39 2 292 299 1:CAS:528: DC%2BD3MXpt1WhtLk%3D 11759294
155. A Svobodova A Zdarilova D Walterova J Vostalova 2007 Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes Journal of Dermatological Science 48 3 213 224 1:CAS:528:DC%2BD2sXht1KgtrrO 17689055
156. RP Singh AK Tyagi J Zhao R Agarwal 2002 Silymarin inhibits growth and causes regression of established skin tumors in sencar mice via modulation of mitogen-activated protein kinases and induction of apoptosis Carcinogenesis 23 3 499 510 1:CAS:528:DC%2BD38Xis1Kntb0%3D 11895866
157. M Gu S Dhanalakshmi RP Singh R Agarwal 2005 Dietary feeding of silibinin prevents early biomarkers of UVB radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis Cancer Epidemiology, Biomarkers & Prevention 14 5 1344 1349 1:CAS:528:DC%2BD2MXktFCkurk%3D
158. S Dhanalakshmi GU Mallikarjuna RP Singh R Agarwal 2004 Silibinin prevents ultraviolet radiation-caused skin damages in SKH-1 hairless mice via a decrease in thymine dimer positive cells and an up-regulation of p53-p21/Cip1 in epidermis Carcinogenesis 25 8 1459 1465 1:CAS:528:DC%2BD2cXmtF2nt7w%3D 15033902
159. M Gu RP Singh S Dhanalakshmi S Mohan R Agarwal 2006 Differential effect of silibinin on E2F transcription factors and associated biological events in chronically UVB-exposed skin versus tumors in SKH-1 hairless mice Molecular Cancer Therapeutics 5 8 2121 2129 1:CAS:528:DC%2BD28XosVansbs%3D 16928834
160. J Zhao R Agarwal 1999 Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: Implications in cancer chemoprevention Carcinogenesis 20 11 2101 2108 1:CAS:528:DyaK1MXns1KjsbY%3D 10545412
161. G Sharma RP Singh DC Chan R Agarwal 2003 Silibinin induces growth inhibition and apoptotic cell death in human lung carcinoma cells Anticancer Research 23 3B 2649 2655 1:CAS:528:DC%2BD3sXmsFyru7o%3D 12894553
162. RP Singh GU Mallikarjuna G Sharma S Dhanalakshmi AK Tyagi DC Chan, et al. 2004 Oral silibinin inhibits lung tumor growth in athymic nude mice and forms a novel chemocombination with doxorubicin targeting nuclear factor kappab-mediated inducible chemoresistance Clinical Cancer Research 10 24 8641 8647 1:CAS:528:DC%2BD2cXhtFGjsL7M 15623648
163. Y Yan Y Wang Q Tan RA Lubet M You 2005 Efficacy of deguelin and silibinin on benzo(a)pyrene-induced lung tumorigenesis in A/J mice Neoplasia 7 12 1053 1057 1:CAS:528:DC%2BD28XptlShsg%3D%3D 16354587 (Pubitemid 44430983)
164. M Kaur B Velmurugan A Tyagi C Agarwal RP Singh R Agarwal 2010 Silibinin suppresses growth of human colorectal carcinoma SW480 cells in culture and xenograft through down-regulation of beta-catenin-dependent signaling Neoplasia 12 5 415 424 1:CAS:528:DC%2BC3cXlvF2ku7w%3D 20454513
165. FS Hogan NK Krishnegowda M Mikhailova MS Kahlenberg 2007 Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer The Journal of Surgical Research 143 1 58 65 1:CAS:528:DC%2BD2sXhtF2htrfP 17950073
166. SH Yang JK Lin CJ Huang WS Chen SY Li JH Chiu 2005 Silibinin inhibits angiogenesis via Flt-1, but not KDR, receptor up-regulation The Journal of Surgical Research 128 1 140 146 1:CAS:528:DC%2BD2MXpsVWlu7o%3D 15993897
167. SH Yang JK Lin WS Chen JH Chiu 2003 Anti-angiogenic effect of silymarin on colon cancer LoVo cell line The Journal of Surgical Research 113 1 133 138 1:CAS:528:DC%2BD3sXms1yjsLs%3D 12943822
168. S Rajamanickam M Kaur B Velmurugan RP Singh R Agarwal 2009 Silibinin suppresses spontaneous tumorigenesis in APC min/+ mouse model by modulating beta-catenin pathway Pharmaceutical Research 26 12 2558 2567 1:CAS:528:DC%2BD1MXhtlCrtb7K 19779968
169. N Sangeetha AJ Felix N Nalini 2009 Silibinin modulates biotransforming microbial enzymes and prevents 1, 2-dimethylhydrazine-induced preneoplastic changes in experimental colon cancer European Journal of Cancer Prevention 18 5 385 394 1:CAS:528:DC%2BD1MXhtV2itLnO 19654488
170. N Sangeetha S Aranganathan N Nalini 2010 Silibinin ameliorates oxidative stress induced aberrant crypt foci and lipid peroxidation in 1, 2 dimethylhydrazine induced rat colon cancer Investigational New Drugs 28 3 225 233 10.1007/s10637-009-9237-5 1:CAS:528:DC%2BC3cXktlGjtLk%3D 19274440
171. B Velmurugan RP Singh A Tyagi R Agarwal 2008 Inhibition of azoxymethane-induced colonic aberrant crypt foci formation by silibinin in male fisher 344 rats Cancer Prevention Research (Philadelphia, PA) 1 5 376 384 1:CAS:528:DC%2BC3cXptFOit7w%3D
172. AK Tyagi C Agarwal DC Chan R Agarwal 2004 Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells Oncology Reports 11 2 493 499 1:CAS:528:DC%2BD2cXhsVGksLY%3D 14719089
173. HJ Wang XF Wei YY Jiang H Huang Y Yang SM Fan, et al. 2010 Silibinin induces the generation of nitric oxide in human breast cancer MCF-7 cells Free Radical Research 44 5 577 584 10.3109/10715761003692495 1:CAS:528: DC%2BC3cXkvVyhur8%3D 20370556
174. X Zi DK Feyes R Agarwal 1998 Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468: Induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins Clinical Cancer Research 4 4 1055 1064 1:CAS:528:DyaK1cXisFeru78%3D 9563902
175. S Kim SH Kim SM Hur SK Lee WW Kim JS Kim, et al. 2009 Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells Journal of Ethnopharmacology 126 2 252 257 10.1016/j.jep.2009.08.032/ S0378-8741(09)00529-7 1:CAS:528:DC%2BD1MXhtlGjt73F 19715751
176. CJ Lin R Sukarieh J Pelletier 2009 Silibinin inhibits translation initiation: Implications for anticancer therapy Molecular Cancer Therapeutics 8 6 1606 1612 10.1158/1535-7163.MCT-08-1152 1:CAS:528:DC%2BD1MXntVKgtro%3D 19509268
177. S Kim JH Choi HI Lim SK Lee WW Kim JS Kim, et al. 2009 Silibinin prevents TPA-induced MMP-9 expression and vegf secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells Phytomedicine 16 6-7 573 580 10.1016/j.phymed.2008.11.006/S0944-7113(08)00219-5 1:CAS:528: DC%2BD1MXotVCgt78%3D 19181503
178. G Scambia R De Vincenzo FO Ranelletti PB Panici G Ferrandina G D'Agostino, et al. 1996 Antiproliferative effect of silybin on gynaecological malignancies: Synergism with cisplatin and doxorubicin European Journal of Cancer 32A 5 877 882 1:CAS:528:DyaK28XjvFyntL8%3D 9081370
179. RD Verschoyle K Brown WP Steward AJ Gescher 2008 Consumption of silibinin, a flavonolignan from milk thistle, and mammary cancer development in the C3(1) SV40 T, t antigen transgenic multiple mammary adenocarcinoma (Tag) mouse Cancer Chemotherapy and Pharmacology 62 2 369 372 1:CAS:528: DC%2BD1cXlvVWiur0%3D 17909802
180. L Qi RP Singh Y Lu R Agarwal GS Harrison A Franzusoff, et al. 2003 Epidermal growth factor receptor mediates silibinin-induced cytotoxicity in a rat glioma cell line Cancer Biology & Therapy 2 5 526 531 1:CAS:528:DC%2BD2cXhtVOiur0%3D
181. KW Kim CH Choi TH Kim CH Kwon JS Woo YK Kim 2009 Silibinin inhibits glioma cell proliferation via Ca2+/ROS/MAPK-dependent mechanism in vitro and glioma tumor growth in vivo Neurochemical Research 34 8 1479 1490 10.1007/s11064-009-9935-6 1:CAS:528:DC%2BD1MXis1Churc%3D 19263218
182. L Varghese C Agarwal A Tyagi RP Singh R Agarwal 2005 Silibinin efficacy against human hepatocellular carcinoma Clinical Cancer Research 11 23 8441 8448 1:CAS:528:DC%2BD2MXht1KjsrbK 16322307
183. E Brandon-Warner JA Sugg LW Schrum IH McKillop 2010 Silibinin inhibits ethanol metabolism and ethanol-dependent cell proliferation in an in vitro model of hepatocellular carcinoma Cancer Letter 291 1 120 129 10.1016/j.canlet.2009. 10.004/S0304-3835(09)00626-0 1:CAS:528:DC%2BC3cXjvFKhtbw%3D
184. P Garcia-Maceira J Mateo 2009 Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: Implications for anticancer therapy Oncogene 28 3 313 324 10.1038/onc.2008.398 1:CAS:528:DC%2BD1MXosVWkug%3D%3D 18978810
185. A Huber P Thongphasuk G Erben WD Lehmann S Tuma W Stremmel, et al. 2008 Significantly greater antioxidant anticancer activities of 2, 3-dehydrosilybin than silybin Biochimica et Biophysica Acta 1780 5 837 847 10.1016/j.bbagen.2007. 12.012/S0304-4165(07)00296-6 1:CAS:528:DC%2BD1cXkvFWqurk%3D 18222181
186. JJ Lah W Cui KQ Hu 2007 Effects and mechanisms of silibinin on human hepatoma cell lines World Journal of Gastroenterology 13 40 5299 5305 1:CAS:528:DC%2BD2sXht1yitLrL 17879397
187. W Cui F Gu KQ Hu 2009 Effects and mechanisms of silibinin on human hepatocellular carcinoma xenografts in nude mice World Journal of Gastroenterology 15 16 1943 1950 1:CAS:528:DC%2BD1MXpsF2ku78%3D 19399925
188. L Zhou P Liu B Chen Y Wang X Wang MC Internati, et al. 2008 Silibinin restores paclitaxel sensitivity to paclitaxel-resistant human ovarian carcinoma cells Anticancer Research 28 2A 1119 1127 1:CAS:528:DC%2BD1cXmt1eht7c%3D 18507063
189. D Gallo S Giacomelli C Ferlini G Raspaglio P Apollonio S Prislei, et al. 2003 Antitumour activity of the silybin-phosphatidylcholine complex, IdB 1016, against human ovarian cancer European Journal of Cancer 39 16 2403 2410 S0959804903006245 1:CAS:528:DC%2BD3sXnvVymur8%3D 14556934
190. A Tyagi RP Singh C Agarwal R Agarwal 2006 Silibinin activates p53-caspase 2 pathway and causes caspase-mediated cleavage of Cip1/p21 in apoptosis induction in bladder transitional-cell papilloma RT4 cells: Evidence for a regulatory loop between p53 and caspase 2 Carcinogenesis 27 11 2269 2280 1:CAS:528:DC%2BD28XhtFKltrnI 16777994
191. RP Singh A Tyagi G Sharma S Mohan R Agarwal 2008 Oral silibinin inhibits in vivo human bladder tumor xenograft growth involving down-regulation of survivin Clinical Cancer Research 14 1 300 308 1:CAS:528:DC%2BD1cXoslKl 18172282
192. A Tyagi C Agarwal G Harrison LM Glode R Agarwal 2004 Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages Carcinogenesis 25 9 1711 1720 10.1093/carcin/bgh180bgh180 1:CAS:528: DC%2BD2cXntFahsL0%3D 15117815
193. AK Tyagi C Agarwal RP Singh KR Shroyer LM Glode R Agarwal 2003 Silibinin down-regulates survivin protein and mRNA expression and causes caspases activation and apoptosis in human bladder transitional-cell papilloma RT4 cells Biochemical and Biophysical Research Communications 312 4 1178 1184 1:CAS:528:DC%2BD3sXpsVSjt7c%3D 14651997
194. A Tyagi K Raina RP Singh M Gu C Agarwal G Harrison, et al. 2007 Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl) nitrosamine induced urinary bladder carcinogenesis in male ICR mice Molecular Cancer Therapeutics 6 12 Pt 1 3248 3255 1:CAS:528:DC%2BD2sXhsVCjsr3F 18089718
195. M Gharagozloo Z Khoshdel Z Amirghofran 2008 The effect of an iron (III) chelator, silybin, on the proliferation and cell cycle of Jurkat cells: A comparison with desferrioxamine European Journal of Pharmacology 589 1-3 1 7 10.1016/j.ejphar.2008.03.059/S0014-999(08)00387-7 1:CAS:528:DC%2BD1cXptVCms7k%3D 18619590
196. M Danilenko Q Wang X Wang J Levy Y Sharoni GP Studzinski 2003 Carnosic acid potentiates the antioxidant and prodifferentiation effects of 1alpha, 25-dihydroxyvitamin D3 in leukemia cells but does not promote elevation of basal levels of intracellular calcium Cancer Research 63 6 1325 1332 1:CAS:528:DC%2BD3sXit1Sgtbk%3D 12649194
197. SN Kang MH Lee KM Kim D Cho TS Kim 2001 Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by silibinin: Involvement of protein kinase C Biochemical Pharmacology 61 12 1487 1495 S0006295201006268 1:CAS:528:DC%2BD3MXjslersLw%3D 11377378
198. CW Cheung DA Vesey DL Nicol DW Johnson 2007 Silibinin inhibits renal cell carcinoma via mechanisms that are independent of insulin-like growth factor-binding protein 3 BJU International 99 2 454 460 1:CAS:528: DC%2BD2sXjt1Kgt7g%3D 17313429
199. CW Cheung PJ Taylor CM Kirkpatrick DA Vesey GC Gobe C Winterford, et al. 2007 Therapeutic value of orally administered silibinin in renal cell carcinoma: Manipulation of insulin-like growth factor binding protein-3 levels BJU International 100 2 438 444 1:CAS:528:DC%2BD2sXpslKjsL4%3D 17617146
200. CI Bang SY Paik DI Sun YH Joo MS Kim 2008 Cell growth inhibition and down-regulation of survivin by silibinin in a laryngeal squamous cell carcinoma cell line The Annals of Otology, Rhinology, and Laryngology 117 10 781 785 18998509
201. S Kim MG Choi HS Lee SK Lee SH Kim WW Kim, et al. 2009 Silibinin suppresses TNF-alpha-induced MMP-9 expression in gastric cancer cells through inhibition of the MAPK pathway Molecules 14 11 4300 4311 10.3390/ molecules14114300 1:CAS:528:DC%2BD1MXhtlOhurbO 19924065