Curcumin mediates anticancer effects by modulating multiple cell signaling pathways

Clinical Science

Volumn 131, Issue 15, 2017, Pages 1781-1799

  Kunnumakkara, Ajaikumar B ^a   Bordoloi, Devivasha ^a   Harsha, Choudhary ^a   Banik, Kishore ^a   Gupta, Subash C ^b   Aggarwal, Bharat B ^c  

^a INDIAN INSTITUTE OF TECHNOLOGY GUWAHATI   (India)

^b BANARAS HINDU UNIVERSITY   (India)

^c Inflammation Research Institute   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BETA CATENIN; CURCUMIN; CYTOKINE; EARLY GROWTH RESPONSE FACTOR 1; ENZYME; GROWTH FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; NOTCH1 RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN; PROTEIN KINASE B; STAT3 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR HIF 1; TRANSCRIPTION FACTOR NRF2; UNCLASSIFIED DRUG; UNTRANSLATED RNA; EGFR PROTEIN, HUMAN; EPIDERMAL GROWTH FACTOR RECEPTOR; STAT3 PROTEIN, HUMAN;

ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER THERAPY; COLON CANCER; COLORECTAL CANCER; FOOD AND DRUG ADMINISTRATION; G2 PHASE CELL CYCLE CHECKPOINT; GLIOBLASTOMA; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; LYMPHOMA; NONHUMAN; OSTEOSARCOMA; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE CANCER; RECTUM CANCER; REVIEW; SIGNAL TRANSDUCTION; SOLID MALIGNANT NEOPLASM; TUMOR GROWTH; TUMOR SUPPRESSOR GENE; UTERINE CERVIX CANCER; WNT SIGNALING PATHWAY; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; NEOPLASMS; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; CURCUMIN; HUMANS; NEOPLASMS; NF-KAPPA B; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR;

EID: 85023603958     PISSN: 01435221     EISSN: 14708736     Source Type: Journal    
DOI: 10.1042/CS20160935     Document Type: Review

References (188)

1. Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of cancer: the next generation. Cell 144, 646-674
2. Bordoloi, D., Roy, N.K., Monisha, J., Padmavathi, G. and Kunnumakkara, A.B. (2016) Multi-targeted agents in cancer cell chemosensitization: What we learnt from curcumin thus far. Recent Pat. Anticancer Drug Discov. 11, 67-97
3. Anand, P., Sundaram, C., Jhurani, S., Kunnumakkara, A.B. and Aggarwal, B.B. (2008) Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Lett. 267, 133-164
4. U.S. Food and Drug Administration, http://fda.gov, accessed on May 25, 2016
5. Goel, A., Jhurani, S. and Aggarwal, B.B. (2008) Multi-targeted therapy by curcumin: how spicy is it? Mol. Nutr. Food Res. 52, 1010-1030
6. Roy, N.K., Deka, A., Bordoloi, D., Mishra, S., Kumar, A.P., Sethi, G. et al. (2016) The potential role of boswellic acids in cancer prevention and treatment. Cancer Lett. 377, 74-86
7. Padmavathi, G., Rathnakaram, S.R., Monisha, J., Bordoloi, D., Roy, N.K. and Kunnumakkara, A.B. (2015) Potential of butein, a tetrahydroxychalcone to obliterate cancer. Phytomed 22, 1163-1171
8. Aggarwal, B., Prasad, S., Sung, B., Krishnan, S. and Guha, S. (2013) Prevention and treatment of colorectal cancer by natural agents from mother nature. Curr. Colorectal Cancer Rep. 9, 37-56
9. Shehzad, A., Lee, J. and Lee, Y.S. (2013) Curcumin in various cancers. Biofactors 39, 56-68
10. Gupta, S.C., Patchva, S. and Aggarwal, B.B. (2013) Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 15, 195-218
11. Prasad, S., Tyagi, A.K. and Aggarwal, B.B. (2014) Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res. Treat. 46, 2-18
12. Prasad, S., Gupta, S.C., Tyagi, A.K. and Aggarwal, B.B. (2014) Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol. Adv. 32, 1053-1064
13. Anand, P., Kunnumakkara, A.B., Newman, R.A. and Aggarwal, B.B. (2007) Bioavailability of curcumin: problems and promises. Mol. Pharm. 4, 807-818
14. Liu, W., Zhai, Y., Heng, X., Che, F.Y., Chen, W., Sun, D. et al. (2016) Oral bioavailability of curcumin: problems and advancements. J. Drug Target. 24, 694-702
15. Kuttan, R., Sudheeran, P.C. and Josph, C.D. (1987) Turmeric and curcumin as topical agents in cancer therapy. Tumori 73, 29-31
16. Ledda, A., Belcaro, G., Dugall, M., Luzzi, R., Scoccianti, M., Togni, S. et al. (2012) Meriva, a lecithinized curcumin delivery system, in the control of benign prostatic hyperplasia: a pilot, product evaluation registry study. Panminerva Med. 54, 17-22
17. Bayet-Robert, M., Kwiatkowski, F., Leheurteur, M., Gachon, F., Planchat, E., Abrial, C. et al. (2010) Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol. Ther. 9, 8-14
18. Cheng, A.L., Hsu, C.H., Lin, J.K., Hsu, M.M., Ho, Y.F., Shen, T.S. et al. (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 21, 2895-2900
19. Basu, P., Dutta, S., Begum, R., Mittal, S., Dutta, P.D., Bharti, A.C. et al. (2013) Clearance of cervical human papillomavirus infection by topical application of curcumin and curcumin containing polyherbal cream: a phase II randomized controlled study. Asian Pac. J. Cancer Prev. 14, 5753-5759
20. Ghalaut, V.S., Sangwan, L., Dahiya, K., Ghalaut, P.S., Dhankhar, R. and Saharan, R. (2012) Effect of imatinib therapy with and without turmeric powder on nitric oxide levels in chronic myeloid leukemia. J. Oncol. Pharm. Pract. 18, 186-190
21. Plummer, S.M., Hill, K.A., Festing, M.F., Steward, W.P., Gescher, A.J. and Sharma, R.A. (2001) Clinical development of leukocyte cyclooxygenase 2 activity as a systemic biomarker for cancer chemopreventive agents. Cancer Epidemiol. Biomarkers Prev. 10, 1295-1299
22. Sharma, R.A., McLelland, H.R., Hill, K.A., Ireson, C.R., Euden, S.A., Manson, M.M. et al. (2001) Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin. Cancer Res. 7, 1894-1900
23. Sharma, R.A., Euden, S.A., Platton, S.L., Cooke, D.N., Shafayat, A., Hewitt, H.R. et al. (2004) Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin. Cancer Res. 10, 6847-6854
24. Garcea, G., Berry, D.P., Jones, D.J., Singh, R., Dennison, A.R., Farmer, P.B. et al. (2005) Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol. Biomarkers Prev. 14, 120-125
25. He, Z.Y., Shi, C.B., Wen, H., Li, F.L., Wang, B.L. and Wang, J. (2011) Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. 29, 208-213
26. Carroll, R.E., Benya, R.V., Turgeon, D.K., Vareed, S., Neuman, M., Rodriguez, L. et al. (2011) Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev. Res. (Phila) 4, 354-364
27. Irving, G.R., Howells, L.M., Sale, S., Kralj-Hans, I., Atkin, W.S., Clark, S.K. et al. (2013) Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration-a clinical pilot study including assessment of patient acceptability. Cancer Prev. Res. (Phila) 6, 119-128
28. Kim, S.G., Veena, M.S., Basak, S.K., Han, E., Tajima, T., Gjertson, D.W. et al. (2011) Curcumin treatment suppresses IKKbeta kinase activity of salivary cells of patients with head and neck cancer: a pilot study. Clin. Cancer Res. 17, 5953-5961
29. Dhillon, N., Aggarwal, B.B., Newman, R.A., Wolff, R.A., Kunnumakkara, A.B., Abbruzzese, J.L. et al. (2008) Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin. Cancer Res. 14, 4491-4499
30. Epelbaum, R., Schaffer, M., Vizel, B., Badmaev, V. and Bar-Sela, G. (2010) Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr. Cancer 62, 1137-1141
31. Kanai, M., Yoshimura, K., Asada, M., Imaizumi, A., Suzuki, C., Matsumoto, S. et al. (2011) A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother. Pharmacol. 68, 157-164
32. Kanai, M., Otsuka, Y., Otsuka, K., Sato, M., Nishimura, T., Mori, Y. et al. (2013) A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients. Cancer Chemother. Pharmacol. 71, 1521-1530
33. Ide, H., Tokiwa, S., Sakamaki, K., Nishio, K., Isotani, S., Muto, S. et al. (2010) Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate 70, 1127-1133
34. Hejazi, J., Rastmanesh, R., Taleban, F.A., Molana, S.H., Hejazi, E. and Ehtejab, G. (2016) Effect of curcumin supplementation during radiotherapy on oxidative status of patients with prostate cancer: a double blinded, randomized, placebo-controlled study. Nutr. Cancer 68, 77-85
35. Belcaro, G., Hosoi, M., Pellegrini, L., Appendino, G., Ippolito, E., Ricci, A. et al. (2014) A controlled study of a lecithinized delivery system of curcumin (Meriva ) to alleviate the adverse effects of cancer treatment. Phytother. Res. 28, 444-450
36. Panahi, Y., Saadat, A., Beiraghdar, F. and Sahebkar, A. (2014) Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother. Res. 28, 1461-1467
37. Clinical Trials.gov-A service of U.S. National Institute of Health, https://clinicaltrials.gov, accessed on June 2, 2016
38. Mimeault, M. and Batra, S.K. (2011) Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy. Chin. Med. 6, 31
39. Shehzad, A. and Lee, Y.S. (2013) Molecular mechanisms of curcumin action: signal transduction. Biofactors 39, 27-36
40. Hatcher, H., Planalp, R., Cho, J., Torti, F.M. and Torti, S.V. (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol. Life Sci. 65, 1631-1652
41. Monisha, J., Roy, N.K., Bordoloi, D., Kumar, A., Golla, R., Kotoky, J. et al. (2016) Nuclear factor kappa B: a potential target to persecute head and neck cancer. Curr. Drug Targets 18, 232-253
42. Sen, R. and Baltimore, D. (1986) Inducibility of kappa immunoglobulin enhancer-binding protein NF-kappa B by a posttranslational mechanism. Cell 47, 921-928
43. Gupta, S.C., Sundaram, C., Reuter, S. and Aggarwal, B.B. (2010) Inhibiting NF-kappaB activation by small molecules as a therapeutic strategy. Biochim. Biophys. Acta 1799, 775-787
44. Sovak, M.A., Bellas, R.E., Kim, D.W., Zanieski, G.J., Rogers, A.E., Traish, A.M. et al. (1997) Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer. J. Clin. Invest. 100, 2952-2960
45. Sun, Y., Ai, X., Shen, S. and Lu, S. (2015) NF-κB-mediated miR-124 suppresses metastasis of non-small-cell lung cancer by targeting MYO10. Oncotarget 6, 8244-8254
46. He, W.A., Berardi, E., Cardillo, V.M., Acharyya, S., Aulino, P., Thomas-Ahner, J. et al. (2013) NF-κB-mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia. J. Clin. Invest. 123, 4821-4835
47. Monisha, J., Padmavathi, G., Roy, N.K., Deka, A., Bordoloi, D., Anip, A. et al. (2016) NF-κB blockers gifted by mother nature: Prospectives in cancer cell chemosensitization. Curr. Pharm. Des. 22, 4173-4200
48. Singh, S. and Aggarwal, B.B. (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J. Biol. Chem. 270, 24995-25000
49. Bharti, A.C., Donato, N. and Aggarwal, B.B. (2003) Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J. Immunol. 171, 3863-3871
50. Philip, S. and Kundu, G.C. (2003) Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha /IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. J. Biol. Chem. 278, 14487-14497
51. Li, L., Braiteh, F.S. and Kurzrock, R. (2005) Liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Cancer 104, 1322-1331
52. Gandhy, S.U., Kim, K., Larsen, L., Rosengren, R.J. and Safe, S. (2012) Curcumin and synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp) transcription factors by targeting microRNAs. BMC Cancer 12, 564
53. Kunnumakkara, A.B., Diagaradjane, P., Anand, P., Harikumar, K.B., Deorukhkar, A., Gelovani, J. et al. (2009) Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX-2, MMP-9, VEGF and CXCR4 expression in an orthotopic mouse model. Int. J. Cancer 125, 2187-2197
54. Lin, Y.G., Kunnumakkara, A.B., Nair, A., Merritt, W.M., Han, L.Y. and Armaiz-Pena, G.N. (2007) Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin. Cancer Res. 13, 3423-3430
55. Shan, X., Li, Y., Meng, X., Wang, P., Jiang, P. and Feng, Q. (2014) Curcumin and (-)-epigallocatechin-3-gallate attenuate acrylamide-induced proliferation in HepG2 cells. Food Chem. Toxicol. 66, 194-202
56. Chen, Y., Shu, W., Chen, W., Wu, Q., Liu, H. and Cui, G. (2007) Curcumin, both histone deacetylase and p300/CBP-specific inhibitor, represses the activity of nuclear factor kappa B and Notch 1 in Raji cells. Basic Clin. Pharmacol. Toxicol. 101, 427-433
57. Nakamura, K., Yasunaga, Y., Segawa, T., Ko, D., Moul, J.W., Srivastava, S. et al. (2002) Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int. J. Oncol. 21, 825-830
58. Zhang, B.Y., Shi, Y.Q., Chen, X., Dai, J., Jiang, Z.F., Li, N. et al. (2013) Protective effect of curcumin against formaldehyde-induced genotoxicity in A549 Cell Lines. J. Appl. Toxicol. 33, 1468-1473
59. Kim, J.M., Noh, E.M., Kwon, K.B., Kim, J.S., You, Y.O., Hwang, J.K. et al. (2012) Curcumin suppresses the TPA-induced invasion through inhibition of PKCa-dependent MMP-expression in MCF-7 human breast cancer cells. Phytomedicine 19, 1085-1092
60. Vadhan-Raj, S., Weber, D., Wang, M., Giralt, S., Alexanian, R., Thomas, S. et al. (2007) Curcumin downregulates NF-B and related genes in patients with multiple myeloma: results of a phase 1/2 study. Blood 110, 357a
61. Kim, S.G., Veena, M.S., Basak, S.K., Han, E., Tajima, T. and Gjertson, D.W. (2011) Curcumin treatment suppresses IKKbeta kinase activity of salivary cells of patients with head and neck cancer: a pilot study. Clin. Cancer Res. 17, 5953-5961
62. Aggarwal, B.B., Sethi, G., Ahn, K.S., Sandur, S.K., Pandey, M.K. and Kunnumakkara, A.B. (2006) Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann. N Y Acad. Sci. 1091, 151-169
63. Gupta, S.C., Kannappan, R., Reuter, S., Kim, J.H. and Aggarwal, B.B. (2011) Chemosensitization of tumors by resveratrol. Ann. N Y Acad. Sci. 1215, 150-160
64. Pandey, A., Vishnoi, K., Mahata, S., Tripathi, S.C., Misra, S.P., Misra, V. et al. (2015) Berberine and curcumin target survivin and STAT3 in gastric cancer cells and synergize actions of standard chemotherapeutic 5-Fluorouracil. Nutr. Cancer 67, 1293-1304
65. Fetoni, A.R., Paciello, F., Mezzogori, D., Rolesi, R., Eramo, S.L., Paludetti, G. et al. (2015) Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling. Br. J. Cancer 113, 1434-1444
66. Wu, L., Guo, L., Liang, Y., Liu, X., Jiang, L. and Wang, L. (2015) Curcumin suppresses stem-like traits of lung cancer cells via inhibiting the JAK2/STAT3 signaling pathway. Oncol. Rep. 34, 3311-3317
67. Wu, J., Lu, W.Y. and Cui, L.L. (2015) Inhibitory effect of curcumin on invasion of skin squamous cell carcinoma A431 cells. Asian Pac. J. Cancer Prev. 16, 2813-2818
68. Alexandrow, M.G., Song, L.J., Altiok, S., Gray, J., Haura, E.B. and Kumar, N.B. (2012) Curcumin: a novel Stat3 pathway inhibitor for chemoprevention of lung cancer. Eur. J. Cancer Prev. 21, 407-412
69. Yang, J.Y., Zhong, X., Yum, H.W., Lee, H.J., Kundu, J.K., Na, H.K. et al. (2013) Curcumin inhibits STAT3 signaling in the colon of dextran sulfate sodium-treated mice. J. Cancer Prev. 18, 186-191
70. Roy, N.K., Bordoloi, D., Monisha, J., Padmavathi, G., Kotoky, J., Golla, R. et al. (2017) Specific targeting of Akt kinase isoforms: Taking the precise path for prevention and treatment of cancer. Curr. Drug Targets 18, 421-435
71. Tan, H.K., Moad, A.I. and Tan, M.L. (2014) The mTOR signalling pathway in cancer and the potential mTOR inhibitory activities of natural phytochemicals. Asian Pac. J. Cancer Prev. 15, 6463-6475
72. Kizhakkayil, J., Thayyullathil, F., Chathoth, S., Hago, A., Patel, M. and Galadari, S. (2010) Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells. Biochem. Biophys. Res. Commun. 394, 476-481
73. Jin, H., Qiao, F., Wang, Y., Xu, Y. and Shang, Y. (2015) Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol. Rep. 34, 2782-2789
74. Xu, Y., Zhang, J., Han, J., Pan, X., Cao, Y., Guo, H. et al. (2012) Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of a1-antitrypsin in lung cancer. Mol. Oncol. 6, 405-417
75. Li, S., Fang, C., Zhang, J., Liu, B., Wei, Z., Fan, X. et al. (2016) Catanionic lipid nanosystems improve pharmacokinetics and anti-lung cancer activity of curcumin. Nanomedicine 12, 1567-1579
76. Bhullar, K.S., Jha, A. and Rupasinghe, H.P. (2015) Novel carbocyclic curcumin analog CUR3d modulates genes involved in multiple apoptosis pathways in human hepatocellular carcinoma cells. Chem. Biol. Interact. 242, 107-122
77. Guan, F., Ding, Y., Zhang, Y., Zhou, Y., Li, M. and Wang, C. (2016) Curcumin suppresses proliferation and migration of MDA-MB-231 breast cancer cells through autophagy-dependent Akt degradation. PLoS ONE 11, e0146553
78. Akkoç, Y., Berrak, Ö., Arsan, E.D., Obakan, P., Çoker-Gürkan, A. and Palavan-Ünsal, N. (2015) Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl2 through activation of autophagy in MCF-7 cells. Biomed. Pharmacother. 71, 161-171
79. Jia, T., Zhang, L., Duan, Y., Zhang, M., Wang, G., Zhang, J. et al. (2014) The differential susceptibilities of MCF-7 and MDA-MB-231 cells to the cytotoxic effects of curcumin are associated with the PI3K/Akt-SKP2-Cip/Kips pathway. Cancer Cell. Int. 14, 126
80. Lai, H.W., Chien, S.Y., Kuo, S.J., Tseng, L.M., Lin, H.Y., Chi, C.W. et al. (2012) The potential utility of curcumin in the treatment of HER-2-overexpressed breast cancer: an in vitro and in vivo comparison study with herceptin. Evid. Based Complement Alternat. Med. 2012, 486568
81. Zhao, Z., Li, C., Xi, H., Gao, Y. and Xu, D. (2015) Curcumin induces apoptosis in pancreatic cancer cells through the induction of forkhead box O1 and inhibition of the PI3K/Akt pathway. Mol. Med. Rep. 12, 5415-5422
82. Li, X.J., Li Y., Z., Jin, C.T., Fan, J. and Li, H.J. (2015) Curcumin induces apoptosis by PTEN/PI3K/AKT pathway in EC109 cells. Zhongguo Ying Yong Sheng Li Xue Za Zhi 31, 174-177
83. Xu, X., Qin, J. and Liu, W. (2014) Curcumin inhibits the invasion of thyroid cancer cells via down-regulation of PI3K/Akt signaling pathway. Gene 546, 226-232
84. Jiang, Q.G., Li, T.Y., Liu, D.N. and Zhang, H.T. (2014) PI3K/Akt pathway involving into apoptosis and invasion in human colon cancer cells LoVo. Mol. Biol. Rep. 41, 3359-3367
85. Rafiee, P., Binion, D.G., Wellner, M., Behmaram, B., Floer, M., Mitton, E. et al. (2010) Modulatory effect of curcumin on survival of irradiated human intestinal microvascular endothelial cells: role of Akt/mTOR and NF-κB. Am J. Physiol. Gastrointest. Liver Physiol. 298, G865-G877
86. Qiao, Q., Jiang, Y. and Li, G. (2013) Inhibition of the PI3K/AKT-NF-κB pathway with curcumin enhanced radiation-induced apoptosis in human Burkitt's lymphoma. J. Pharmacol. Sci. 121, 247-256
87. Lee, J.H., Jang, J.Y., Park, C., Kim, B.W., Choi, Y.H. and Choi, B.T. (2010) Curcumin suppresses alpha-melanocyte stimulating hormone-stimulated melanogenesis in B16F10 cells. Int. J. Mol. Med. 26, 101-106
88. Choi, B.H., Kim, C.G., Bae, Y.S., Lim, Y., Lee, Y.H. and Shin, S.Y. (2008) p21 Waf1/Cip1 expression by curcumin in U-87MG human glioma cells: role of early growth response-1 expression. Cancer Res. 68, 1369-1377
89. Patel, B.B., Gupta, D., Elliott, A.A., Sengupta, V., Yu, Y. and Majumdar, A.P. (2010) Curcumin targets FOLFOX-surviving colon cancer cells via inhibition of EGFRs and IGF-1R. Anticancer Res. 30, 319-325
90. Zhao, G., Han, X., Zheng, S., Li, Z., Sha, Y., Ni, J. et al. (2016) Curcumin induces autophagy, inhibits proliferation and invasion by downregulating AKT/mTOR signaling pathway in human melanoma cells. Oncol. Rep. 35, 1065-1074
91. Du, Y., Long, Q., Zhang, L., Shi, Y., Liu, X., Li, X. et al. (2015) Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1a signaling. Int. J. Oncol. 47, 2064-2072
92. Li, B., Takeda, T., Tsuiji, K., Wong, T.F., Tadakawa, M., Kondo, A. et al. (2013) Curcumin induces cross-regulation between autophagy and apoptosis in uterine leiomyosarcoma cells. Int. J. Gynecol. Cancer 23, 803-808
93. Clark, C.A., McEachern, M.D., Shah, S.H., Rong, Y., Rong, X., Smelley, C.L. et al. (2010) Curcumin inhibits carcinogen and nicotine-induced Mammalian target of rapamycin pathway activation in head and neck squamous cell carcinoma. Cancer Prev. Res. (Phila.) 3, 1586-1595
94. Guo, Y., Li, Y., Shan, Q., He, G., Lin, J. and Gong, Y. (2015) Curcumin potentiates the anti-leukemia effects of imatinib by downregulation of the AKT/mTOR pathway and BCR/ABL gene expression in Ph+ acute lymphoblastic leukemia. Int. J. Biochem. Cell Biol. 65, 1-11
95. Kondo, A., Takeda, T., Li, B., Tsuiji, K., Kitamura, M., Wong, T.F. et al. (2012) Epigallocatechin-3-gallate potentiates curcumin's ability to suppress uterine leiomyosarcoma cell growth and induce apoptosis. Int. J. Clin. Oncol. 18, 380-388
96. Wong, T.F., Takeda, T., Li, B., Tsuiji, K., Kitamura, M., Kondo, A. et al. (2011) Curcumin disrupts uterine leiomyosarcoma cells through AKT-mTOR pathway inhibition. Gynecol. Oncol. 122, 141-148
97. Mathur, A., Abd Elmageed, Z.Y., Liu, X., Kostochka M., L., Zhang, H., Abdel-Mageed, A.B. et al. (2014) Subverting ER-stress towards apoptosis by nelfinavir and curcumin coexposure augments docetaxel efficacy in castration resistant prostate cancer cells. PLoS ONE 9, e103109
98. Chen, T.Y., Xu, F., Kong, Y.Y., Wen, F., Xie, F.Y., Wan, L.G. et al. (2013) Effect of curcumin combined with ATRA on differentiation of ATRA-resistant acute promyelocytic leukemia cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 21, 895-898
99. Yu, T., Li, J., Qiu, Y. and Sun, H. (2012) 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) facilitates curcumin-induced melanoma cell apoptosis by enhancing ceramide accumulation, JNK activation, and inhibiting PI3K/AKT activation. Mol. Cell Biochem. 361, 47-54
100. Yarden, Y. (2001) The EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities. Eur. J. Cancer 37, S3-S8
101. Starok, M., Preira, P., Vayssade, M., Haupt, K., Salomé, L. and Rossi, C. (2015) EGFR inhibition by curcumin in cancer cells: a dual mode of action. Biomacromolecules 16, 1634-1642
102. Bojko, A., Cierniak, A., Adamczyk, A. and Ligeza, J. (2015) Modulatory effects of curcumin and tyrphostins (AG494 and AG1478) on growth regulation and viability of LN229 human brain cancer cells. Nutr. Cancer. 67, 1170-1182
103. Wada, K., Lee, J.Y., Hung, H.Y., Shi, Q., Lin, L., Zhao, Y. et al. (2015) Novel curcumin analogs to overcome EGFR-TKI lung adenocarcinoma drug resistance and reduce EGFR-TKI-induced GI adverse effects. Bioorg. Med. Chem. 23, 1507-1514
104. Li, S., Liu, Z., Zhu, F., Fan, X., Wu, X., Zhao, H. et al. (2013) Curcumin lowers erlotinib resistance in non-small cell lung carcinoma cells with mutated EGF receptor. Oncol. Res. 21, 137-144
105. Lev-Ari, S., Starr, A., Vexler, A., Karaush, V., Loew, V., Greif, J. et al. (2006) Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity. Anticancer Res. 26, 4423-4430
106. Zhen, L., Fan, D., Yi, X., Cao, X., Chen, D. and Wang, L. (2014) Curcumin inhibits oral squamous cell carcinoma proliferation and invasion via EGFR signaling pathways. Int. J. Clin. Exp. Pathol. 7, 6438-6446
107. Chen, J.W., Tang, Y.L., Liu, H., Zhu, Z.Y., Lü, D., Geng, N. et al. (2011) Anti-proliferative and anti-metastatic effects of curcumin on oral cancer cells. Hua Xi Kou Qiang Yi Xue Za Zhi 29, 83-86
108. Khafif, A., Lev-Ari, S., Vexler, A., Barnea, I., Starr, A., Karaush, V. et al. (2009) Curcumin: a potential radio-enhancer in head and neck cancer. Laryngoscope 119, 2019-2026
109. Yoysungnoen-Chintana, P., Bhattarakosol, P. and Patumraj, S. (2014) Antitumor and antiangiogenic activities of curcumin in cervical cancer xenografts in nude mice. Biomed. Res. Int. 2014, 817972
110. Wang, S., Yu, S., Shi, W., Ge, L., Yu, X., Fan, J. et al. (2011) Curcumin inhibits the migration and invasion of mouse hepatoma Hca-F cells through down-regulating caveolin-1 expression and epidermal growth factor receptor signaling. IUBMB Life 63, 775-782
111. Chen, A., Xu, J. and Johnson, A.C. (2006) Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene 25, 278-287
112. Sun, X.D., Liu, X.E. and Huang, D.S. (2012) Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression. Mol. Med. Rep. 6, 1267-1270
113. Somers-Edgar, T.J., Scandlyn, M.J., Stuart, E.C., Le Nedelec, M.J., Valentine, S.P. and Rosengren, R.J. (2008) The combination of epigallocatechin gallate and curcumin suppresses ER alpha-breast cancer cell growth in vitro and in vivo. Int. J. Cancer. 122, 1966-1971
114. Ji, C., Cao, C., Lu, S., Kivlin, R., Amaral, A., Kouttab, N. et al. (2008) Curcumin attenuates EGF-induced AQP3 up-regulation and cell migration in human ovarian cancer cells. Cancer Chemother. Pharmacol. 62, 857-865
115. Chadalapaka, G., Jutooru, I., Burghardt, R. and Safe, S. (2010) Drugs that target specificity proteins downregulate epidermal growth factor receptor in bladder cancer cells. Mol. Cancer Res. 8, 739-750
116. Soung, Y.H. and Chung, J. (2011) Curcumin inhibition of the functional interaction between integrin α6β4 and the epidermal growth factor receptor. Mol. Cancer Ther. 10, 883-891
117. Sivanantham, B., Sethuraman, S. and Krishnan, U.M. (2016) Combinatorial effects of curcumin with an anti-neoplastic agent on head and neck squamous cell carcinoma through the regulation of EGFR-ERK1/2 and apoptotic signaling pathways. ACS Comb. Sci. 18, 22-35
118. Zhan, Y., Chen, Y., Liu, R., Zhang, H. and Zhang, Y. (2014) Potentiation of paclitaxel activity by curcumin in human breast cancer cell by modulating apoptosis and inhibiting EGFR signaling. Arch. Pharm. Res. 37, 1086-1095
119. Lee, J.Y., Lee, Y.M., Chang, G.C., Yu, S.L., Hsieh, W.Y., Chen, J.J. et al. (2011) Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy. PLoS ONE 6, e23756
120. Lin, H.P., Kuo, L.K. and Chuu, C.P. (2012) Combined treatment of curcumin and small molecule inhibitors suppresses proliferation of A549 and H1299 human non-small-cell lung cancer cells. Phytother. Res. 26, 122-126
121. Majumdar, A.P., Banerjee, S., Nautiyal, J., Patel, B.B., Patel, V., Du, J. et al. (2009) Curcumin synergizes with resveratrol to inhibit colon cancer. Nutr. Cancer 61, 544-553
122. Kim, J.H., Xu, C., Keum, Y.S., Reddy, B., Conney, A. and Kong, A.N. (2005) Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with beta-phenylethyl isothiocyanate and curcumin. Carcinogenesis. 27, 475-482
123. Kwak, M.K. and Kensler, T.W. (2010) Targeting NRF2 signaling for cancer chemoprevention. Toxicol. Appl. Pharmacol. 244, 66-76
124. Das, L. and Vinayak, M. (2015) Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer. PLoS ONE 10, e0124000
125. Boyanapalli, S.S., Paredes-Gonzalez, X., Fuentes, F., Zhang, C., Guo, Y., Pung, D. et al. (2014) Nrf2 knockout attenuates the anti-inflammatory effects of phenethyl isothiocyanate and curcumin. Chem. Res. Toxicol. 27, 2036-2043
126. Chen, B., Zhang, Y., Wang, Y., Rao, J., Jiang, X. and Xu, Z. (2014) Curcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression. J. Steroid Biochem. Mol. Biol. 143, 11-18
127. Khor, T.O., Huang, Y., Wu, T.Y., Shu, L., Lee, J. and Kong, A.N. (2011) Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation. Biochem. Pharmacol. 82, 1073-1078
128. Zhang, S.N., Yong, Q., Wu, X.L. and Liu, X.P. (2014) Synergism inhibition of curcumin combined with cisplatin on T24 bladder carcinoma cells and its related mechanism. Zhong Yao Cai. 37, 2043-2046
129. Chen, J., Wang, F.L. and Chen, W.D. (2014) Modulation of apoptosis-related cell signaling pathways by curcumin as a strategy to inhibit tumor progression. Mol. Biol. Rep. 41, 4583-4594
130. Roy, S., Levi, E., Majumdar, A.P. and Sarkar, F.H. (2012) Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF. J. Hematol. Oncol. 5, 58
131. Subramaniam, D., Ponnurangam, S., Ramamoorthy, P., Standing, D., Battafarano, R.J., Anant, S. et al. (2012) Curcumin induces cell death in esophageal cancer cells through modulating Notch signaling. PLoS One 7, e30590
132. Subramaniam, D., Ramalingam, S., Houchen, C.W. and Anant, S. (2010) Cancer stem cells: a novel paradigm for cancer prevention and treatment. Mini Rev. Med. Chem. 10, 359-371
133. Li, Y., Wicha, M.S., Schwartz, S.J. and Sun, D. (2011) Implications of cancer stem cell theory for cancer chemoprevention by natural dietary compounds. J. Nutr. Biochem. 22, 799-806
134. Li, Y., Wang, J., Li, X., Jia, Y., Huai, L., He, K. et al. (2014) Role of the Wilms' tumor 1 gene in the aberrant biological behavior of leukemic cells and the related mechanisms. Oncol. Rep. 32, 2680-2686
135. Glienke, W., Maute, L., Wicht, J. and Bergmann, L (2009) Wilms' tumour gene 1 (WT1) as a target in curcumin treatment of pancreatic cancer cells. Eur. J. Cancer 45, 874-880
136. Anuchapreeda, S., Limtrakul, P., Thanarattanakorn, P., Sittipreechacharn, S. and Chanarat, P. (2006) Inhibitory effect of curcumin on WT1 gene expression in patient leukemic cells. Arch. Pharm. Res. 29, 80-87
137. Gao, S.M., Yang, J.J., Chen, C.Q., Chen, J.J., Ye, L.P., Wang, L.Y. et al. (2012) Pure curcumin decreases the expression of WT1 by upregulation of miR-15a and miR-16-1 in leukemic cells. J. Exp. Clin. Cancer Res. 31, 27
138. Li, Y., Li, X.Y., Wang, L., Tian, Z., Rao, Q., Jia, H.R. et al. (2010) Biological characteristics of Wt1 gene in relation to Ph(+) leukemia cell line K562. Zhongguo Shi Yan Xue Ye Xue Za Zhi 18, 564-569
139. Anuchapreeda, S., Tima, S., Duangrat, C. and Limtrakul, P. (2008) Effect of pure curcumin, demethoxycurcumin, and bisdemethoxycurcumin on WT1 gene expression in leukemic cell lines. Cancer Chemother Pharmacol. 62, 585-594
140. Karin, M., Zg., Liu and Zandi, E. (1997) AP-1 function and regulation. Curr. Opin. Cell. Biol. 9, 240-246
141. Shaulian, E. and Karin, M. (2002) AP-1 as a regulator of cell life and death. Nat. Cell Biol. 4, E131-E136
142. Liu, S., Wang, Z., Hu, Z., Zeng, X., Li, Y., Su, Y. et al. (2011) Anti-tumor activity of curcumin against androgen-independent prostate cancer cells via inhibition of NF-κB and AP-1 pathway in vitro. J. Huazhong Univ. Sci. Technol. Med. Sci. 31, 530-534
143. Das, L. and Vinayak, M. (2014) Curcumin attenuates carcinogenesis by down regulating proinflammatory cytokine interleukin-1 (IL-1α and IL-1β) via modulation of AP-1 and NF-IL6 in lymphoma bearing mice. Int. Immunopharmacol. 20, 141-147
144. Yang, C.W., Chang, C.L., Lee, H.C., Chi, C.W., Pan, J.P. and Yang, W.C. (2012) Curcumin induces the apoptosis of human monocytic leukemia THP-1 cells via the activation of JNK/ERK pathways. BMC Complement Altern. Med. 12, 22
145. Mudduluru, G., George-William, J.N., Muppala, S., Asangani, I.A., Kumarswamy, R., Nelson, L.D. et al. (2011) Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer. Biosci. Rep. 31, 185-197
146. Wang, G.L., Jiang, B.H., Rue, E.A. and Semenza, G.L. (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. U.S.A. 92, 5510-5514
147. Yang, J., Zhang, L., Erbel, P.J., Gardner, K.H., Ding, K., Garcia, J.A. et al. (2005) Functions of the Per/ARNT/Sim domains of the hypoxia-inducible factor. J. Biol. Chem. 280, 36047-36054
148. Chapman-Smith, A., Lutwyche, J.K. and Whitelaw, M.L. (2004) Contribution of the Per/Arnt/Sim (PAS) domains to DNA binding by the basic helix-loop-helix PAS transcriptional regulators. J. Biol. Chem. 279, 5353-5362
149. Semenza, G.L. (1998) Hypoxia-inducible factor 1: master regulator of O2 homeostasis. Curr. Opin. Genet. Dev. 8, 588-594
150. Upadhyay, J., Kesharwani, R.K. and Misra, K. (2009) Comparative study of antioxidants as cancer preventives through inhibition of HIF-1 alpha activity. Bioinformation 4, 233-236
151. Bae, M.K., Kim, S.H., Jeong, J.W., Lee, Y.M., Kim, H.S., Kim, S.R. et al. (2006) Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1. Oncol. Rep. 15, 1557-1562
152. Shan, B., Schaaf, C., Schmidt, A., Lucia, K., Buchfelder, M., Losa, M. et al. (2012) Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas. J. Endocrinol. 214, 389-398
153. Choi, H., Chun, Y.S., Kim, S.W., Kim, M.S. and Park, J.W. (2006) Curcumin inhibits hypoxia-inducible factor-1 by degrading aryl hydrocarbon receptor nuclear translocator: a mechanism of tumor growth inhibition. Mol. Pharmacol. 70, 1664-1671
154. Lee, S.S., Tsai, C.H., Yang, S.F., Ho, Y.C. and Chang, Y.C. (2010) Hypoxia inducible factor-1a expression in areca quid chewing-associated oral squamous cell carcinomas. Oral. Dis. 16, 696-701
155. Ye, M.X., Zhao, Y.L., Li, Y., Miao, Q., Li, Z.K., Ren, X.L. et al. (2012) Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma A549/DDP cell apoptosis through HIF-1a and caspase-3 mechanisms. Phytomed 19, 779-787
156. Logan, C.Y. and Nusse, R. (2004) The Wnt signaling pathway in development and disease. Annu. Rev. Cell Dev. Biol. 20, 781-810
157. Prasad, C.P., Rath, G., Mathur, S., Bhatnagar, D. and Ralhan, R. (2009) Potent growth suppressive activity of curcumin in human breast cancer cells: Modulation of Wnt/beta-catenin signaling. Chem. Biol. Interact. 181, 263-271
158. Mukherjee, S., Mazumdar, M., Chakraborty, S., Manna, A., Saha, S., Khan, P. et al. (2014) Curcumin inhibits breast cancer stem cell migration by amplifying the E-cadherin/β-catenin negative feedback loop. Stem Cell Res. Ther. 5, 116
159. Somers-Edgar, T.J., Taurin, S., Larsen, L., Chandramouli, A., Nelson, M.A. and Rosengren, R.J. (2011) Mechanisms for the activity of heterocyclic cyclohexanone curcumin derivatives in estrogen receptor negative human breast cancer cell lines. Invest. New Drugs 29, 87-97
160. Sundram, V., Chauhan, S.C., Ebeling, M. and Jaggi, M. (2012) Curcumin attenuates β-catenin signaling in prostate cancer cells through activation of protein kinase D1. PLoS ONE 7, e35368
161. Choi, H.Y., Lim, J.E. and Hong, J.H. (2010) Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells. Prostate Cancer Prostatic Dis. 13, 343-349
162. Yallapu, M.M., Khan, S., Maher, D.M., Ebeling, M.C., Sundram, V., Chauhan, N. et al. (2014) Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer. Biomaterials 35, 8635-8648
163. Lu, Y., Wei, C. and Xi, Z. (2014) Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt/β-catenin pathway. In Vitro Cell. Dev. Biol. Anim. 50, 840-850
164. Wang, J.B., Qi, L.L., Zheng, S.D., Wang, H.Z. and Wu, T.X. (2009) Curcumin suppresses PPARdelta expression and related genes in HT-29 cells. World J. Gastroenterol. 15, 1346-1352
165. Jaiswal, A.S., Marlow, B.P., Gupta, N. and Narayan, S. (2002) Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene 21, 8414-8427
166. Kim, T.D., Fuchs, J.R., Schwartz, E., Abdelhamid, D., Etter, J., Berry, W.L. et al. (2014) Pro-growth role of the JMJD2C histone demethylase in HCT-116 colon cancer cells and identification of curcuminoids as JMJD2 inhibitors. Am. J. Transl. Res. 6, 236-247
167. Lai, C.S., Wu, J.C., Yu, S.F., Badmaev, V., Nagabhushanam, K., Ho, C.T. et al. (2011) Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis. Mol. Nutr. Food Res. 55, 1819-1828
168. Alizadeh, A.M., Khaniki, M., Azizian, S., Mohaghgheghi, M.A., Sadeghizadeh, M. and Najafi, F. (2012) Chemoprevention of azoxymethane-initiated colon cancer in rat by using a novel polymeric nanocarrier-curcumin. Eur. J. Pharmacol. 689, 226-232
169. Liu, C., Calogero, A., Ragona, G., Adamson, E. and Mercola, D. (1996) EGR-1, the reluctant suppression factor: EGR-1 is known to function in the regulation of growth, differentiation, and also has significant tumor suppressor activity and a mechanism involving the induction of TGF-beta1 is postulated to account for this suppressor activity. Crit. Rev. Oncog. 7, 101-125
170. Baron, V., Adamson, E.D., Calogero, A., Ragona, G. and Mercola, D. (2006) The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1,PTEN, p53, and fibronectin. Cancer Gene. Ther. 13, 115-124
171. Aggarwal, B.B., Kumar, A. and Bharti, A.C. (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 23, 363-398
172. Choi, B.H., Kim, C.G., Bae, Y.S., Lim, Y., Lee, Y.H. and Shin, S.Y. (2008) p21 Waf1/Cip1 expression by curcumin in U-87MG human glioma cells: role of early growth response-1 expression. Cancer Res. 68, 1369-1377
173. Han, S.S., Chung, S.T., Robertson, D.A., Ranjan, D. and Bondada, S. (1999) Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-kappa B, and p53. Clin. Immunol. 93, 152-161
174. Tahira, A.C., Kubrusly, M.S., Faria, M.F., Dazzani, B., Fonseca, R.S., Maracaja-Coutinho, V. et al. (2011) Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer. Mol. Cancer 10, 141
175. Yan, X., Hu, Z., Feng, Y., Hu, X., Yuan, J., Zhao, S.D. et al. (2015) Comprehensive genomic characterization of long non-coding RNAs across human cancers. Cancer Cell 28, 529-540
176. Ohtsuka, M., Ling, H., Doki, Y., Mori, M. and Calin, G.A. (2015) MicroRNA processing and human cancer. J. Clin. Med. 4, 1651-1667
177. Chen, Y., Fu, L.L., Wen, X., Liu, B., Huang, J., Wang, J.H. et al. (2014) Oncogenic and tumor suppressive roles of microRNAs in apoptosis and autophagy. Apoptosis 19, 1177-1189
178. Spizzo, R., Almeida, M.I., Colombatti, A. and Calin, G.A. (2012) Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene 31, 4577-4587
179. Gupta, S.C., Kismali, G. and Aggarwal, B.B. (2013) Curcumin, a component of turmeric: from farm to pharmacy. Biofactors 39, 2-13
180. Sun, M., Estrov, Z., Ji, Y., Coombes, K.R., Harris, D.H. and Kurzrock, R. (2008) Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol. Cancer Ther. 7, 464-473
181. Zhang, J., Zhang, T., Ti, X., Shi, J., Wu, C., Ren, X. et al. (2010) Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway. Biochem. Biophys. Res. Commun. 399, 1-6
182. Ali, S., Ahmad, A., Banerjee, S., Padhye, S., Dominiak, K., Schaffert, J.M. et al. (2010) Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF. Cancer Res. 70, 3606-3617
183. Zamani, M., Sadeghizadeh, M., Behmanesh, M. and Najafi, F. (2015) Dendrosomal curcumin increases expression of the long non-coding RNA gene MEG3 via up-regulation of epi-miRs in hepatocellular cancer. Phytomed 22, 961-967
184. Pei, C.S., Wu, H.Y., Fan, F.T., Wu, Y., Shen, C.S. and Pan, L.Q. (2014) Influence of curcumin on HOTAIR-mediated migration of human renal cell carcinoma cells. Asian Pac. J. Cancer Prev. 15, 4239-4243
185. Wang, Q., Fan, H., Liu, Y., Yin, Z., Cai, H., Liu, J. et al. (2014) Curcumin enhances the radiosensitivity in nasopharyngeal carcinoma cells involving the reversal of differentially expressed long non-coding RNAs. Int. J. Oncol. 44, 858-864
186. Shehzad, A., Ul Islam, S., Lee, J. and Lee, Y.S. (2014) Prostaglandin E2 reverses curcumin-induced inhibition of survival signal pathways in human colorectal carcinoma (HCT-15) cell lines. Mol. Cells 37, 899-906
187. Wang, S.H., Lin, P.Y., Chiu, Y.C., Huang, J.S., Kuo, Y.T., Wu, J.C. et al. (2015) Curcumin-mediated HDAC inhibition suppresses the DNA damage response and contributes to increased DNA damage sensitivity. PLoS ONE 10, e0134110
188. Shao, Z.M., Shen, Z.Z., Liu, C.H., Sartippour, M.R., Go, V.L., Heber, D. et al. (2002) Curcumin exerts multiple suppressive effects on human breast carcinoma cells. Int. J. Cancer 98, 234-240