Fucoxanthin and its metabolite fucoxanthinol in cancer prevention and treatment

Marine Drugs

Volumn 13, Issue 8, 2015, Pages 4784-4798

  Martin, Luc J ^a  

^a UNIVERSITÉ DE MONCTON   (Canada)

Author keywords

Apoptosis; Cancer; Fucoxanthin; Fucoxanthinol; Viability

Indexed keywords

DRUG METABOLITE; FUCOXANTHIN; FUCOXANTHINOL; GELATINASE B; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 45; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERSTITIAL COLLAGENASE; JANUS KINASE; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; PROTEIN KINASE B; RETINOBLASTOMA PROTEIN; STAT PROTEIN; STAT3 PROTEIN; TRANSCRIPTION FACTOR SOX9; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; BETA CAROTENE; XANTHOPHYLL;

ANTIANGIOGENIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; BLADDER CANCER; BREAST CANCER; CANCER PREVENTION; CELL CYCLE ARREST; DIGESTIVE SYSTEM CANCER; DRUG MECHANISM; HUMAN; LEUKEMIA; LIVER CANCER; LUNG CANCER; LYMPHOMA; NEOPLASM; NONHUMAN; OSTEOSARCOMA; PROTEIN EXPRESSION; REGULATORY MECHANISM; SKIN CANCER; UTERINE CERVIX CANCER; ANALOGS AND DERIVATIVES; ANIMAL; DRUG EFFECTS; NEOPLASMS; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BETA CAROTENE; HUMANS; NEOPLASMS; SIGNAL TRANSDUCTION; XANTHOPHYLLS;

EID: 84940398397     PISSN: None     EISSN: 16603397     Source Type: Journal    
DOI: 10.3390/md13084784     Document Type: Article

References (93)

1. Matsuno, T. Aquatic animal carotenoids. Fish. Sci. 2001, 67, 771-783.
2. Beppu, F.; Niwano, Y.; Tsukui, T.; Hosokawa, M.; Miyashita, K. Single and repeated oral dose toxicity study of fucoxanthin (FX), a marine carotenoid, in mice. J. Toxicol. Sci. 2009, 34, 501-510.
3. Beppu, F.; Niwano, Y.; Sato, E.; Kohno, M.; Tsukui, T.; Hosokawa, M.; Miyashita, K. In vitro and in vivo evaluation of mutagenicity of fucoxanthin (FX) and its metabolite fucoxanthinol (FXOH). J. Toxicol. Sci. 2009, 34, 693-698.
4. Airanthi, M. K. W. A.; Hosokawa, M.; Miyashita, K. Comparative antioxidant activity of edible Japanese brown seaweeds. J. Food Sci. 2011, 76, C104-C111.
5. D'Orazio, N.; Gemello, E.; Gammone, M. A.; De Girolamo, M.; Ficoneri, C.; Riccioni, G. Fucoxantin: A treasure from the sea. Mar. Drugs 2012, 10, 604-616.
6. Asai, A.; Sugawara, T.; Ono, H.; Nagao, A. Biotransformation of fucoxanthinol into amarouciaxanthin A in mice and HepG2 cells: Formation and cytotoxicity of fucoxanthin metabolites. Drug Metab. Dispos. 2004, 32, 205-211.
7. Sugawara, T.; Baskaran, V.; Tsuzuki, W.; Nagao, A. Brown algae fucoxanthin is hydrolyzed to fucoxanthinol during absorption by Caco-2 human intestinal cells and mice. J. Nutr. 2002, 132, 946-951.
8. Nishino, H.; Murakoshi, M.; Tokuda, H.; Satomi, Y. Cancer prevention by carotenoids. Arch. Biochem. Biophys. 2009, 483, 165-168.
9. Nishikawa, S.; Hosokawa, M.; Miyashita, K. Fucoxanthin promotes translocation and induction of glucose transporter 4 in skeletal muscles of diabetic/obese KK-Ay mice. Phytomedicine 2012, 19, 389-394.
10. Maeda, H.; Hosokawa, M.; Sashima, T.; Funayama, K.; Miyashita, K. Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues. Biochem. Biophys. Res. Commun. 2005, 332, 392-397.
11. Kim, K. N.; Heo, S. J.; Yoon, W. J.; Kang, S. M.; Ahn, G.; Yi, T. H.; Jeon, Y. J. Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-κB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages. Eur. J. Pharmacol. 2010, 649, 369-375.
12. Shiratori, K.; Ohgami, K.; Ilieva, I.; Jin, X. H.; Koyama, Y.; Miyashita, K.; Yoshida, K.; Kase, S.; Ohno, S. Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Exp. Eye Res. 2005, 81, 422-428.
13. Zhang, S.; Hunter, D. J.; Forman, M. R.; Rosner, B. A.; Speizer, F. E.; Colditz, G. A.; Manson, J. E.; Hankinson, S. E.; Willett, W. C. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J. Natl. Cancer Inst. 1999, 91, 547-556.
14. Slattery, M. L.; Benson, J.; Curtin, K.; Ma, K. N.; Schaeffer, D.; Potter, J. D. Carotenoids and colon cancer. Am. J. Clin. Nutr. 2000, 71, 575-582.
15. Le Marchand, L.; Hankin, J. H.; Kolonel, L. N.; Beecher, G. R.; Wilkens, L. R.; Zhao, L. P. Intake of specific carotenoids and lung cancer risk. Cancer Epidemiol. Biomark. Prev. 1993, 2, 183-187.
16. Das, S. K.; Hashimoto, T.; Shimizu, K.; Yoshida, T.; Sakai, T.; Sowa, Y.; Komoto, A.; Kanazawa, K. Fucoxanthin induces cell cycle arrest at G0/G1 phase in human colon carcinoma cells through up-regulation of p21WAF1/Cip1. Biochim. Biophys. Acta 2005, 1726, 328-335.
17. Kotake-Nara, E.; Asai, A.; Nagao, A. Neoxanthin and fucoxanthin induce apoptosis in PC-3 human prostate cancer cells. Cancer Lett. 2005, 220, 75-84.
18. Kumar, S. R.; Hosokawa, M.; Miyashita, K. Fucoxanthin: A marine carotenoid exerting anti-cancer effects by affecting multiple mechanisms. Mar. Drugs 2013, 11, 5130-5147.
19. Ganesan, P.; Matsubara, K.; Sugawara, T.; Hirata, T. Marine algal carotenoids inhibit angiogenesis by down-regulating FGF-2-mediated intracellular signals in vascular endothelial cells. Mol. Cell. Biochem. 2013, 380, doi:10.1007/s11010-013-1651-5.
20. Wang, D.; Mayo, M. W.; Baldwin, A. S. Basic fibroblast growth factor transcriptional autoregulation requires EGR-1. Oncogene 1997, 14, 2291-2299.
21. Liu, C. L.; Huang, Y. S.; Hosokawa, M.; Miyashita, K.; Hu, M. L. Inhibition of proliferation of a hepatoma cell line by fucoxanthin in relation to cell cycle arrest and enhanced gap junctional intercellular communication. Chem. Biol. Interact. 2009, 182, 165-172.
22. Rokkaku, T.; Kimura, R.; Ishikawa, C.; Yasumoto, T.; Senba, M.; Kanaya, F.; Mori, N. Anticancer effects of marine carotenoids, fucoxanthin and its deacetylated product, fucoxanthinol, on osteosarcoma. Int. J. Oncol. 2013, 43, 1176-1186.
23. Wang, J.; Chen, S.; Xu, S.; Yu, X.; Ma, D.; Hu, X.; Cao, X. In vivo induction of apoptosis by fucoxanthin, a marine carotenoid, associated with down-regulating STAT3/EGFR signaling in sarcoma 180 (S180) xenografts-bearing mice. Mar. Drugs 2012, 10, 2055-2068.
24. Jin, S.; Pang, R. P.; Shen, J. N.; Huang, G.; Wang, J.; Zhou, J. G. Grifolin induces apoptosis via inhibition of PI3K/AKT signalling pathway in human osteosarcoma cells. Apoptosis 2007, 12, 1317-1326.
25. Tokunaga, E.; Oki, E.; Egashira, A.; Sadanaga, N.; Morita, M.; Kakeji, Y.; Maehara, Y. Deregulation of the Akt pathway in human cancer. Curr. Cancer Drug Targets 2008, 8, 27-36.
26. Romashkova, J. A.; Makarov, S. S. NF-κB is a target of AKT in anti-apoptotic PDGF signalling. Nature 1999, 401, 86-90.
27. Morin, P. J. β-Catenin signaling and cancer. BioEssays 1999, 21, 1021-1030.
28. Behrens, J. Control of β-Catenin signaling in tumor development. Ann. N. Y. Acad. Sci. 2000, 910, 21-33; discussion 33-35.
29. Kimura, R.; Ishikawa, C.; Rokkaku, T.; Janknecht, R.; Mori, N. Phosphorylated c-Jun. and Fra-1 induce matrix metalloproteinase-1 and thereby regulate invasion activity of 143B osteosarcoma cells. Biochim. Biophys. Acta 2011, 1813, 1543-1553.
30. Desrivières, S.; Kunz, C.; Barash, I.; Vafaizadeh, V.; Borghouts, C.; Groner, B. The biological functions of the versatile transcription factors STAT3 and STAT5 and new strategies for their targeted inhibition. J. Mammary Gland Biol. Neoplasia 2006, 11, 75-87.
31. Kisseleva, T.; Bhattacharya, S.; Braunstein, J.; Schindler, C. W. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 2002, 285, 1-24.
32. Kim, K. N.; Heo, S. J.; Kang, S. M.; Ahn, G.; Jeon, Y. J. Fucoxanthin induces apoptosis in human leukemia HL-60 cells through a ROS-mediated Bcl-xL pathway. Toxicol. Vitro 2010, 24, 1648-1654.
33. Konishi, I.; Hosokawa, M.; Sashima, T.; Kobayashi, H.; Miyashita, K. Halocynthiaxanthin and fucoxanthinol isolated from Halocynthia roretzi induce apoptosis in human leukemia, breast and colon cancer cells. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 2006, 142, 53-59.
34. Kotake-Nara, E.; Terasaki, M.; Nagao, A. Characterization of apoptosis induced by fucoxanthin in human promyelocytic leukemia cells. Biosci. Biotechnol. Biochem. 2005, 69, 224-227.
35. Yamamoto, K.; Ishikawa, C.; Katano, H.; Yasumoto, T.; Mori, N. Fucoxanthin and its deacetylated product, fucoxanthinol, induce apoptosis of primary effusion lymphomas. Cancer Lett. 2011, 300, 225-234.
36. Lee, J. Y.; Lee, M. S.; Choi, H. J.; Choi, J. W.; Shin, T.; Woo, H. C.; Kim, J. I.; Kim, H. R. Hexane fraction from Laminaria japonica exerts anti-inflammatory effects on lipopolysaccharide-stimulated RAW 264.7 macrophages via inhibiting NF-κB pathway. Eur. J. Nutr. 2013, 52, 409-421.
37. Ishikawa, C.; Tafuku, S.; Kadekaru, T.; Sawada, S.; Tomita, M.; Okudaira, T.; Nakazato, T.; Toda, T.; Uchihara, J. N.; Taira, N.; et al. Anti-adult T-cell leukemia effects of brown algae fucoxanthin and its deacetylated product, fucoxanthinol. Int. J. Cancer 2008, 123, 2702-2712.
38. Tamura, R. E.; De Vasconcellos, J. F.; Sarkar, D.; Libermann, T. A.; Fisher, P. B.; Zerbini, L. F. GADD45 proteins: Central players in tumorigenesis. Curr. Mol. Med. 2012, 12, 634-651.
39. Tafuku, S.; Ishikawa, C.; Yasumoto, T.; Mori, N. Anti-neoplastic effects of fucoxanthin and its deacetylated product, fucoxanthinol, on Burkitt's and Hodgkin's lymphoma cells. Oncol. Rep. 2012, 28, 1512-1518.
40. Min, K. B.; Min, J. Y. Serum carotenoid levels and risk of lung cancer death in US adults. Cancer Sci. 2014, 105, 736-743.
41. Chung, T. W.; Choi, H. J.; Lee, J. Y.; Jeong, H. S.; Kim, C. H.; Joo, M.; Choi, J. Y.; Han, C. W.; Kim, S. Y.; Choi, J. S.; et al. Marine algal fucoxanthin inhibits the metastatic potential of cancer cells. Biochem. Biophys. Res. Commun. 2013, 439, 580-585.
42. Wang, S. K.; Li, Y.; White, W. L.; Lu, J. Extracts from New Zealand Undaria pinnatifida Containing Fucoxanthin as Potential Functional Biomaterials against Cancer in Vitro. J. Funct. Biomater. 2014, 5, 29-42.
43. Smith, B. D.; Smith, G. L.; Hurria, A.; Hortobagyi, G. N.; Buchholz, T. A. Future of cancer incidence in the United States: Burdens upon an aging, changing nation. J. Clin. Oncol. 2009, 27, 2758-2765.
44. Kotake-Nara, E.; Kushiro, M.; Zhang, H.; Sugawara, T.; Miyashita, K.; Nagao, A. Carotenoids affect proliferation of human prostate cancer cells. J. Nutr. 2001, 131, 3303-3306.
45. Satomi, Y.; Nishino, H. Implication of mitogen-activated protein kinase in the induction of G1 cell cycle arrest and gadd45 expression by the carotenoid fucoxanthin in human cancer cells. Biochim. Biophys. Acta 2009, 1790, 260-266.
46. Satomi, Y. Fucoxanthin induces GADD45A expression and G1 arrest with SAPK/JNK activation in LNCap human prostate cancer cells. Anticancer Res. 2012, 32, 807-813.
47. Yoshiko, S.; Hoyoku, N. Fucoxanthin, a natural carotenoid, induces G1 arrest and GADD45 gene expression in human cancer cells. In Vivo 2007, 21, 305-309.
48. Yin, F.; Bruemmer, D.; Blaschke, F.; Hsueh, W. A.; Law, R. E.; Herle, A. J. V. Signaling pathways involved in induction of GADD45 gene expression and apoptosis by troglitazone in human MCF-7 breast carcinoma cells. Oncogene 2004, 23, 4614-4623.
49. Zhang, J.; Dhakal, I. B.; Zhao, Z.; Li, L. Trends in mortality from cancers of the breast, colon, prostate, esophagus, and stomach in East Asia: Role of nutrition transition. Eur. J. Cancer Prev. 2012, 21, 480-489.
50. Hosokawa, M.; Kudo, M.; Maeda, H.; Kohno, H.; Tanaka, T.; Miyashita, K. Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARgamma ligand, troglitazone, on colon cancer cells. Biochim. Biophys. Acta 2004, 1675, 113-119.
51. Duronio, R. J.; Xiong, Y. Signaling pathways that control cell proliferation. Cold Spring Harb. Perspect. Biol. 2013, 5, a008904, doi:10.1101/cshperspect.a008904.
52. Dick, F. A.; Rubin, S. M. Molecular mechanisms underlying RB protein function. Nat. Rev. Mol. Cell Biol. 2013, 14, 297-306.
53. Yu, R. X.; Hu, X. M.; Xu, S. Q.; Jiang, Z. J.; Yang, W. Effects of fucoxanthin on proliferation and apoptosis in human gastric adenocarcinoma MGC-803 cells via JAK/STAT signal pathway. Eur. J. Pharmacol. 2011, 657, 10-19.
54. Eid, S. Y.; El-Readi, M. Z.; Wink, M. Carotenoids reverse multidrug resistance in cancer cells by interfering with ABC-transporters. Phytomedicine 2012, 19, 977-987.
55. Choi, Y. H.; Yu, A. M. ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development. Curr. Pharm. Des. 2014, 20, 793-807.
56. Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2012. CA Cancer J. Clin. 2012, 62, 10-29.
57. Liu, C. L.; Lim, Y. P.; Hu, M. L. Fucoxanthin enhances cisplatin-induced cytotoxicity via NFκB-mediated pathway and downregulates DNA repair gene expression in human hepatoma HepG2 cells. Mar. Drugs 2013, 11, 50-66.
58. Das, S. K.; Hashimoto, T.; Kanazawa, K. Growth inhibition of human hepatic carcinoma HepG2 cells by fucoxanthin is associated with down-regulation of cyclin D. Biochim. Biophys. Acta 2008, 1780, 743-749.
59. Pondugula, S. R.; Mani, S. Pregnane xenobiotic receptor in cancer pathogenesis and therapeutic response. Cancer Lett. 2013, 328, 1-9.
60. Wang, H.; Venkatesh, M.; Li, H.; Goetz, R.; Mukherjee, S.; Biswas, A.; Zhu, L.; Kaubisch, A.; Wang, L.; Pullman, J.; et al. Pregnane X receptor activation induces FGF19-dependent tumor aggressiveness in humans and mice. J. Clin. Investig. 2011, 121, 3220-3232.
61. Liu, C. L.; Lim, Y. P.; Hu, M. L. Fucoxanthin attenuates rifampin-induced cytochrome P450 3A4 (CYP3A4) and multiple drug resistance 1 (MDR1) gene expression through pregnane X receptor (PXR)-mediated pathways in human hepatoma HepG2 and colon adenocarcinoma LS174T cells. Mar. Drugs 2012, 10, 242-257.
62. Zhang, Z.; Zhang, P.; Hamada, M.; Takahashi, S.; Xing, G.; Liu, J.; Sugiura, N. Potential chemoprevention effect of dietary fucoxanthin on urinary bladder cancer EJ-1 cell line. Oncol. Rep. 2008, 20, 1099-1103.
63. Wang, L.; Zeng, Y.; Liu, Y.; Hu, X.; Li, S.; Wang, Y.; Li, L.; Lei, Z.; Zhang, Z. Fucoxanthin induces growth arrest and apoptosis in human bladder cancer T24 cells by up-regulation of p21 and down-regulation of mortalin. Acta Biochim. Biophys. Sin. 2014, 46, 877-884.
64. Kachuri, L.; De, P.; Ellison, L. F.; Semenciw, R. Advisory Committee on Canadian Cancer Statistics Cancer incidence, mortality and survival trends in Canada, 1970-2007. Chronic Dis. Inj. Can. 2013, 33, 69-80.
65. Kim, K.-N.; Ahn, G.; Heo, S. J.; Kang, S. M.; Kang, M. C.; Yang, H. M.; Kim, D.; Roh, S. W.; Kim, S. K.; Jeon, B. T.; et al. Inhibition of tumor growth in vitro and in vivo by fucoxanthin against melanoma B16F10 cells. Environ. Toxicol. Pharmacol. 2013, 35, 39-46.
66. Shimoda, H.; Tanaka, J.; Shan, S. J.; Maoka, T. Anti-pigmentary activity of fucoxanthin and its influence on skin mRNA expression of melanogenic molecules. J. Pharm. Pharmacol. 2010, 62, 1137-1145.
67. Hou, L.; Gao, C.; Chen, L.; Hu, G.; Xie, S. Essential role of autophagy in fucoxanthin-induced cytotoxicity to human epithelial cervical cancer HeLa cells. Acta Pharmacol. Sin. 2013, 34, 1403-1410.
68. Ye, G.; Lu, Q.; Zhao, W.; Du, D.; Jin, L.; Liu, Y. Fucoxanthin induces apoptosis in human cervical cancer cell line HeLa via PI3K/Akt pathway. Tumour Biol. 2014, 35, 11261-11267.
69. Lordan, S.; Ross, R. P.; Stanton, C. Marine bioactives as functional food ingredients: Potential to reduce the incidence of chronic diseases. Mar. Drugs 2011, 9, 1056-1100.
70. Peng, J.; Yuan, J. P.; Wu, C. F.; Wang, J. H. Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: Metabolism and bioactivities relevant to human health. Mar. Drugs 2011, 9, 1806-1828.
71. Tanaka, T.; Shnimizu, M.; Moriwaki, H. Cancer chemoprevention by carotenoids. Molecules 2012, 17, 3202-3242.
72. Ayyad, S. E. N.; Ezmirly, S. T.; Basaif, S. A.; Alarif, W. M.; Badria, A. F.; Badria, F. A. Antioxidant, cytotoxic, antitumor, and protective DNA damage metabolites from the red sea brown alga Sargassum sp. Pharmacogn. Res. 2011, 3, 160-165.
73. Rwigemera, A.; Mamelona, J.; Martin, L. J. Inhibitory effects of fucoxanthinol on the viability of human breast cancer cell lines MCF-7 and MDA-MB-231 are correlated with modulation of the NF-κB pathway. Cell Biol. Toxicol. 2014, 30, 157-167.
74. Rwigemera, A.; Mamelona, J.; Martin, L. J. Comparative Effects Between Fucoxanthinol and its Precursor Fucoxanthin on Viability and Apoptosis of Breast Cancer Cell Lines MCF-7 and MDA-MB-231. Anticancer Res. 2015, 35, 207-219.
75. Frasor, J.; Weaver, A.; Pradhan, M.; Dai, Y.; Miller, L. D.; Lin, C. Y.; Stanculescu, A. Positive cross-talk between estrogen receptor and NF-κB in breast cancer. Cancer Res. 2009, 69, 8918-8925.
76. Kalaitzidis, D.; Gilmore, T. D. Transcription factor cross-talk: The estrogen receptor and NF-κB. Trends Endocrinol. Metab. 2005, 16, 46-52.
77. Zubair, A.; Frieri, M. Role of nuclear factor-κB in breast and colorectal cancer. Curr. Allergy Asthma Rep. 2013, 13, 44-49.
78. Cogswell, P. C.; Guttridge, D. C.; Funkhouser, W. K.; Baldwin, A. S., Jr. Selective activation of NF-κB subunits in human breast cancer: Potential roles for NF-κB2/p52 and for Bcl-3. Oncogene 2000, 19, 1123-1131.
79. Dejardin, E.; Bonizzi, G.; Bellahcène, A.; Castronovo, V.; Merville, M. P.; Bours, V. Highly-expressed p100/p52 (NFKB2) sequesters other NF-κB-related proteins in the cytoplasm of human breast cancer cells. Oncogene 1995, 11, 1835-1841.
80. Nakshatri, H.; Bhat-Nakshatri, P.; Martin, D. A.; Goulet, R. J., Jr.; Sledge, G. W., Jr. Constitutive activation of NF-κB during progression of breast cancer to hormone-independent growth. Mol. Cell. Biol. 1997, 17, 3629-3639.
81. Fan, Y.; Dutta, J.; Gupta, N.; Fan, G.; Gélinas, C. Regulation of programmed cell death by NF-κB and its role in tumorigenesis and therapy. Adv. Exp. Med. Biol. 2008, 615, 223-250.
82. Wang, C. Y.; Cusack, J. C.; Liu, R.; Baldwin, A. S. Control of inducible chemoresistance: Enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB. Nat. Med. 1999, 5, 412-417.
83. Wang, C. Y.; Mayo, M. W.; Baldwin, A. S. TNF- and cancer therapy-induced apoptosis: Potentiation by inhibition of NF-κB. Science 1996, 274, 784-787.
84. Saegusa, M.; Hashimura, M.; Suzuki, E.; Yoshida, T.; Kuwata, T. Transcriptional up-regulation of Sox9 by NF-κB in endometrial carcinoma cells, modulating cell proliferation through alteration in the p14 (ARF)/p53/p21 (WAF1) pathway. Am. J. Pathol. 2012, 181, 684-692.
85. Sun, L.; Mathews, L. A.; Cabarcas, S. M.; Zhang, X.; Yang, A.; Zhang, Y.; Young, M. R.; Klarmann, K. D.; Keller, J. R.; Farrar, W. L. Epigenetic Regulation of SOX9 by the NF-κB Signaling Pathway in Pancreatic Cancer Stem Cells. Stem Cells 2013, 31, 1454-1466.
86. Matheu, A.; Collado, M.; Wise, C.; Manterola, L.; Cekaite, L.; Tye, A. J.; Canamero, M.; Bujanda, L.; Schedl, A.; Cheah, K. S. E.; et al. Oncogenicity of the developmental transcription factor Sox9. Cancer Res. 2012, 72, 1301-1315.
87. Chakravarty, G.; Moroz, K.; Makridakis, N. M.; Lloyd, S. A.; Galvez, S. E.; Canavello, P. R.; Lacey, M. R.; Agrawal, K.; Mondal, D. Prognostic significance of cytoplasmic SOX9 in invasive ductal carcinoma and metastatic breast cancer. Exp. Biol. Med. 2011, 236, 145-155.
88. Bellizzi, A.; Mangia, A.; Chiriatti, A.; Petroni, S.; Quaranta, M.; Schittulli, F.; Malfettone, A.; Cardone, R. A.; Paradiso, A.; Reshkin, S. J. RhoA protein expression in primary breast cancers and matched lymphocytes is associated with progression of the disease. Intl. J. Mol. Med. 2008, 22, 25-31.
89. Katoh, M. Cancer genomics and genetics of FGFR2 (Review). Intl. J. Oncol. 2008, 33, 233-237.
90. Kubo, M.; Nakamura, M.; Tasaki, A.; Yamanaka, N.; Nakashima, H.; Nomura, M.; Kuroki, S.; Katano, M. Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res. 2004, 64, 6071-6074.
91. Moore, L. D.; Isayeva, T.; Siegal, G. P.; Ponnazhagan, S. Silencing of transforming growth factor-β1 in situ by RNA interference for breast cancer: Implications for proliferation and migration in vitro and metastasis in vivo. Clin. Cancer Res. 2008, 14, 4961-4970.
92. Xu, Z.; Wang, W.; Deng, C. X.; Man, Y. G. Aberrant p63 and WT-1 expression in myoepithelial cells of pregnancy-associated breast cancer: Implications for tumor aggressiveness and invasiveness. Intl. J. Biol. Sci. 2009, 5, 82-96.
93. Zardawi, S. J.; O'Toole, S. A.; Sutherland, R. L.; Musgrove, E. A. Dysregulation of Hedgehog, Wnt and Notch signalling pathways in breast cancer. Histol. Histopathol. 2009, 24, 385-398.