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Tumor Biology

, Volume 37, Issue 10, pp 13017–13028 | Cite as

Molecular targets of curcumin for cancer therapy: an updated review

  • Pandima Devi Kasi
  • Rajavel Tamilselvam
  • Krystyna Skalicka-Woźniak
  • Seyed Fazel Nabavi
  • Maria Daglia
  • Anupam Bishayee
  • Hamidreza Pazoki-toroudi
  • Seyed Mohammad Nabavi
Review

Abstract

In recent years, natural edible products have been found to be important therapeutic agents for the treatment of chronic human diseases including cancer, cardiovascular disease, and neurodegeneration. Curcumin is a well-known diarylheptanoid constituent of turmeric which possesses anticancer effects under both pre-clinical and clinical conditions. Moreover, it is well known that the anticancer effects of curcumin are primarily due to the activation of apoptotic pathways in the cancer cells as well as inhibition of tumor microenvironments like inflammation, angiogenesis, and tumor metastasis. In particular, extensive studies have demonstrated that curcumin targets numerous therapeutically important cancer signaling pathways such as p53, Ras, PI3K, AKT, Wnt-β catenin, mTOR and so on. Clinical studies also suggested that either curcumin alone or as combination with other drugs possess promising anticancer effect in cancer patients without causing any adverse effects. In this article, we critically review the available scientific evidence on the molecular targets of curcumin for the treatment of different types of cancer. In addition, we also discuss its chemistry, sources, bioavailability, and future research directions.

Keywords

Anticancer Curcumin Polyphenol Turmeric 

Notes

Acknowledgments

The Indian authors KPD and TR gratefully acknowledge the computational and bioinformatics facility provided by the Alagappa University Bioinformatics Infrastructure Facility (funded by Department of Biotechnology, Government of India; Grant No. BT/BI/25/015/2012).

Compliance with ethical standards

Conflicts of interest

None.

References

  1. 1.
    Ruddon RW. Cancer biology. New York: Oxford University Press; 2007.Google Scholar
  2. 2.
    Russo M, Russo GL, Daglia M, Kasi PD, Ravi S, Nabavi SF, et al. Understanding genistein in cancer: the “good” and the “bad” effects: a review. Food Chem. 2016;196:589–600.PubMedCrossRefGoogle Scholar
  3. 3.
    Saranath D, Khanna A. Current status of cancer burden: global and Indian scenario. Biomed Res J. 2014;1(1):1–5.Google Scholar
  4. 4.
    Devi KP, Rajavel T, Nabavi SF, Setzer WN, Ahmadi A, Mansouri K, et al. Hesperidin: a promising anticancer agent from nature. Ind Crop Prod. 2015;76:582–9.CrossRefGoogle Scholar
  5. 5.
    Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. 2008;25(9):2097–116.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358(11):1148–59.PubMedCrossRefGoogle Scholar
  7. 7.
    Taby R, Issa JPJ. Cancer epigenetics. CA Cancer J Clin. 2010;60(6):376–92.PubMedCrossRefGoogle Scholar
  8. 8.
    Perera FP. Environment and cancer: who are susceptible? Science. 1997;278(5340):1068–73.PubMedCrossRefGoogle Scholar
  9. 9.
    Ames BN, Gold LS, Willett WC. The causes and prevention of cancer. Proc Natl Acad Sci. 1995;92(12):5258–65.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Boffetta P. Human cancer from environmental pollutants: the epidemiological evidence. Mutat Res Genet Toxicol Environ Mutagen. 2006;608(2):157–62.CrossRefGoogle Scholar
  11. 11.
    Williams GH, Stoeber K. The cell cycle and cancer. J Pathol. 2012;226(2):352–64.PubMedCrossRefGoogle Scholar
  12. 12.
    Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003;36(3):131–49.PubMedCrossRefGoogle Scholar
  13. 13.
    Curti V, Capelli E, Boschi F, Nabavi SF, Bongiorno AI, Habtemariam S, et al. Modulation of human miR-17–3p expression by methyl 3-O-methyl gallate as explanation of its in vivo protective activities. Mol Nutr Food Res. 2014;58(9):1776–84.PubMedCrossRefGoogle Scholar
  14. 14.
    Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012;75(3):311–35.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Fulda S. Modulation of apoptosis by natural products for cancer therapy. Planta Med. 2010;76(11):1075–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Tan W, Lu J, Huang M, Li Y, Chen M, Wu G, et al. Anti-cancer natural products isolated from chinese medicinal herbs. Chin Med. 2011;6(1):27.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Cragg GM, Kingston DG, Newman DJ. Anticancer agents from natural products. Boca Raton: CRC Press; 2011.CrossRefGoogle Scholar
  18. 18.
    Demain AL, Vaishnav P. Natural products for cancer chemotherapy. Microb Biotechnol. 2011;4(6):687–99.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Mehta RG, Murillo G, Naithani R, Peng X. Cancer chemoprevention by natural products: how far have we come? Pharm Res. 2010;27(6):950–61.PubMedCrossRefGoogle Scholar
  20. 20.
    Nabavi SM, Nabavi SF, Eslami S, Moghaddam AH. In vivo protective effects of quercetin against sodium fluoride-induced oxidative stress in the hepatic tissue. Food Chem. 2012;132(2):931–5.CrossRefGoogle Scholar
  21. 21.
    Nabavi SF, Nabavi SM, Habtemariam S, Moghaddam AH, Sureda A, Jafari M, et al. Hepatoprotective effect of gallic acid isolated from Peltiphyllum peltatum against sodium fluoride-induced oxidative stress. Ind Crop Prod. 2013;44:50–5.CrossRefGoogle Scholar
  22. 22.
    Nabavi SM, Marchese A, Izadi M, Curti V, Daglia M, Nabavi SF. Plants belonging to the genus Thymus as antibacterial agents: from farm to pharmacy. Food Chem. 2015;173:339–47.PubMedCrossRefGoogle Scholar
  23. 23.
    Alinezhad H, Azimi R, Zare M, Ebrahimzadeh MA, Eslami S, Nabavi SF, et al. Antioxidant and antihemolytic activities of ethanolic extract of flowers, leaves, and stems of Hyssopus officinalis L. Var. Angustifolius. Int J Food Prop. 2013;16(5):1169–78.CrossRefGoogle Scholar
  24. 24.
    Nabavi SF, Nabavi SM, Mirzaei M, Moghaddam AH. Protective effect of quercetin against sodium fluoride induced oxidative stress in rat’s heart. Food Funct. 2012;3(4):437–41.PubMedCrossRefGoogle Scholar
  25. 25.
    Nabavi SF, Nabavi SM, Ebrahimzadeh MA, Eslami B, Jafari N. In vitro antioxidant and antihemolytic activities of hydroalcoholic extracts of Allium scabriscapum Boiss. & Ky. Aerial parts and bulbs. Int J Food Prop. 2013;16(4):713–22.CrossRefGoogle Scholar
  26. 26.
    Nabavi SF, Russo GL, Daglia M, Nabavi SM. Role of quercetin as an alternative for obesity treatment: you are what you eat! Food Chem. 2015;179:305–10.PubMedCrossRefGoogle Scholar
  27. 27.
    Di Lorenzo A, Nabavi SF, Sureda A, Moghaddam AH, Khanjani S, Arcidiaco P, et al. Antidepressive-like effects and antioxidant activity of green tea and GABA green tea in a mouse model of post-stroke depression. Mol Nutr Food Res. 2016;60:566–79.Google Scholar
  28. 28.
    Nabavi SF, Nabavi SM, Moghaddam AH, Naqinezhad A, Bigdellou R, Mohammadzadeh S. Protective effects of Allium paradoxum against gentamicin-induced nephrotoxicity in mice. Food Funct. 2012;3(1):28–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Nabavi SF, Nabavi SM, Ebrahimzadeh MA, Jafari N, Yazdanpanah S. Biological activities of freshwater algae, Spirogyra singularis Nordstedt. J Aquat Food Prod Technol. 2013;22(1):58–65.CrossRefGoogle Scholar
  30. 30.
    Nabavi SF, Daglia M, Moghaddam AH, Habtemariam S, Nabavi SM. Curcumin and liver disease: from chemistry to medicine. Compr Rev Food Sci Food Saf. 2014;13(1):62–77.CrossRefGoogle Scholar
  31. 31.
    Ghosh S, Banerjee S, Sil PC. The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: a recent update. Food Chem Toxicol. 2015;83:111–24.PubMedCrossRefGoogle Scholar
  32. 32.
    Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol. 2009;41(1):40–59.PubMedCrossRefGoogle Scholar
  33. 33.
    Darvesh AS, Carroll RT, Bishayee A, Novotny NA, Geldenhuys WJ, Van der Schyf CJ. Curcumin and neurodegenerative diseases: a perspective. Expert Opin Investig Drugs. 2012;21(8):1123–40.PubMedCrossRefGoogle Scholar
  34. 34.
    Darvesh AS, Aggarwal BB, Bishayee A. Curcumin and liver cancer: a review. Curr Pharm Biotechnol. 2012;13(1):218–28.PubMedCrossRefGoogle Scholar
  35. 35.
    Sinha D, Biswas J, Sung B, Aggarwal BB, Bishayee A. Chemopreventive and chemotherapeutic potential of curcumin in breast cancer. Curr Drug Targets. 2012;13(14):1799–819.PubMedCrossRefGoogle Scholar
  36. 36.
    Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin AR, Amin A, et al. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin Cancer Biol. 2015;35(Suppl):S276-–304.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Shehzad A, Wahid F, Lee YS. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm. 2010;343(9):489–99.CrossRefGoogle Scholar
  38. 38.
    Oyagbemi AA, Saba AB, Ibraheem AO. Curcumin: from food spice to cancer prevention. Asian Pac J Cancer Prev. 2009;10(6):963–7.PubMedGoogle Scholar
  39. 39.
    Goel A, Jhurani S, Aggarwal BB. Multi-targeted therapy by curcumin: how spicy is it? Mol Nutr Food Res. 2008;52(9):1010–30.PubMedCrossRefGoogle Scholar
  40. 40.
    Thangapazham RL, Sharma A, Maheshwari RK. Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J. 2006;8(3):E443–E9.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Shehzad A, Lee YS. Molecular mechanisms of curcumin action: signal transduction. Biofactors. 2013;39(1):27–36.PubMedCrossRefGoogle Scholar
  42. 42.
    Tuorkey M. Curcumin a potent cancer preventive agent: mechanisms of cancer cell killing. Interv Med Appl Sci. 2014;6(4):139–46.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Schneider C, Gordon ON, Edwards RL, Luis PB. Degradation of curcumin: from mechanism to biological implications. J Agric Food Chem. 2015;63(35):7606–14.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Ahmed K, Li Y, McClements DJ, Xiao H. Nanoemulsion-and emulsion-based delivery systems for curcumin: encapsulation and release properties. Food Chem. 2012;132(2):799–807.CrossRefGoogle Scholar
  45. 45.
    Tønnesen HH, Karlsen J. Studies on curcumin and curcuminoids. Z Lebensm Unters Forsch. 1985;180(5):402–4.PubMedCrossRefGoogle Scholar
  46. 46.
    Tønnesen HH, Másson M, Loftsson T. Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability. Int J Pharm. 2002;244(1):127–35.PubMedCrossRefGoogle Scholar
  47. 47.
    Leung MH, Colangelo H, Kee TW. Encapsulation of curcumin in cationic micelles suppresses alkaline hydrolysis. Langmuir. 2008;24(11):5672–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Liu A, Lou H, Zhao L, Fan P. Validated LC/MS/MS assay for curcumin and tetrahydrocurcumin in rat plasma and application to pharmacokinetic study of phospholipid complex of curcumin. J Pharm Biomed Anal. 2006;40(3):720–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcumin–phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm. 2007;330(1):155–63.PubMedCrossRefGoogle Scholar
  50. 50.
    Wang X, Jiang Y, Wang Y-W, Huang M-T, Ho C-T, Huang Q. Enhancing anti-inflammation activity of curcumin through O/W nanoemulsions. Food Chem. 2008;108(2):419–24.PubMedCrossRefGoogle Scholar
  51. 51.
    Yu H, Huang Q. Enhanced in vitro anti-cancer activity of curcumin encapsulated in hydrophobically modified starch. Food Chem. 2010;119(2):669–74.CrossRefGoogle Scholar
  52. 52.
    Borrin TR, Georges EL, Moraes IC, Pinho SC. Curcumin-loaded nanoemulsions produced by the emulsion inversion point (EIP) method: an evaluation of process parameters and physico-chemical stability. J Food Eng. 2016;169:1–9.CrossRefGoogle Scholar
  53. 53.
    Li J, Lee IW, Shin GH, Chen X, Park HJ. Curcumin-Eudragit® E PO solid dispersion: a simple and potent method to solve the problems of curcumin. Eur J Pharm Biopharm. 2015;94:322–32.PubMedCrossRefGoogle Scholar
  54. 54.
    Patil S, Choudhary B, Rathore A, Roy K, Mahadik K. Enhanced oral bioavailability and anticancer activity of novel curcumin loaded mixed micelles in human lung cancer cells. Phytomedicine. 2015;22(12):1103–11.PubMedCrossRefGoogle Scholar
  55. 55.
    John PC, Mews M, Moore R. Cyclin/Cdk complexes: their involvement in cell cycle progression and mitotic division. Protoplasma. 2001;216(3–4):119–42.PubMedCrossRefGoogle Scholar
  56. 56.
    Lim T-G, Lee S-Y, Huang Z, Chen H, Jung SK, Bode AM, et al. Curcumin suppresses proliferation of colon cancer cells by targeting CDK2. Cancer Prev Res. 2014;7(4):466–74.CrossRefGoogle Scholar
  57. 57.
    Srivastava RK, Chen Q, Siddiqui I, Sarva K, Shankar S. Linkage of curcumin-induced cell cycle arrest and apoptosis by cyclin-dependent kinase inhibitor p21/WAF1/CIP1. Cell Cycle. 2007;6(23):2953–61.PubMedCrossRefGoogle Scholar
  58. 58.
    Choi BH, Kim CG, Bae Y-S, Lim Y, Lee YH, Shin SY. p21Waf1/Cip1 expression by curcumin in U-87MG human glioma cells: role of early growth response-1 expression. Cancer Res. 2008;68(5):1369–77.PubMedCrossRefGoogle Scholar
  59. 59.
    Krishnaraju K, Nguyen HQ, Liebermann DA, Hoffman B. The zinc finger transcription factor Egr-1 potentiates macrophage differentiation of hematopoietic cells. Mol Cell Biol. 1995;15(10):5499–507.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Krones-Herzig A, Mittal S, Yule K, Liang H, English C, Urcis R, et al. Early growth response 1 acts as a tumor suppressor in vivo and in vitro via regulation of p53. Cancer Res. 2005;65(12):5133–43.PubMedCrossRefGoogle Scholar
  61. 61.
    Mazumder S, DuPree E, Almasan A. A dual role of cyclin E in cell proliferation and apotosis may provide a target for cancer therapy. Curr Cancer Drug Targets. 2004;4(1):65–75.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Keyomarsi K, Tucker SL, Buchholz TA, Callister M, Ding Y, Hortobagyi GN, et al. Cyclin E and survival in patients with breast cancer. N Engl J Med. 2002;347(20):1566–75.PubMedCrossRefGoogle Scholar
  63. 63.
    Aggarwal BB, Banerjee S, Bharadwaj U, Sung B, Shishodia S, Sethi G. Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochem Pharmacol. 2007;73(7):1024–32.PubMedCrossRefGoogle Scholar
  64. 64.
    Lee DS, Lee MK, Kim JH. Curcumin induces cell cycle arrest and apoptosis in human osteosarcoma (HOS) cells. Anticancer Res. 2009;29(12):5039–44.PubMedGoogle Scholar
  65. 65.
    Park MJ, Kim EH, Park IC, Lee HC, Woo SH, Lee JY, et al. Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53. Int J Oncol. 2002;21(2):379–83.PubMedGoogle Scholar
  66. 66.
    Choudhuri T, Pal S, Das T, Sa G. Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner. J Biol Chem. 2005;280(20):20059–68.PubMedCrossRefGoogle Scholar
  67. 67.
    Li X, Kikuchi K, Takano Y. ING genes work as tumor suppressor genes in the carcinogenesis of head and neck squamous cell carcinoma. J Oncol. 2010;2011:963614.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Wang Y, Wang T, Han Y, Wu H, Zhao W, Tong D, et al. Reduced ING4 expression is associated with the malignancy of human bladder. Urol Int. 2015;94(4):464–71.PubMedCrossRefGoogle Scholar
  69. 69.
    Liu E, Wu J, Cao W, Zhang J, Liu W, Jiang X, et al. Curcumin induces G2/M cell cycle arrest in a p53-dependent manner and upregulates ING4 expression in human glioma. J Neuro-Oncol. 2007;85(3):263–70.CrossRefGoogle Scholar
  70. 70.
    Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Muller PA, Vousden KH. Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer Cell. 2014;25(3):304–17.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G. Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Lett. 2002;512(1–3):334–40.PubMedCrossRefGoogle Scholar
  73. 73.
    Jee SH, Shen SC, Kuo ML, Tseng CR, Chiu HC. Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. J Investig Dermatol. 1998;111(4):656–61.PubMedCrossRefGoogle Scholar
  74. 74.
    Jiang MC, Yang-Yen HF, Yen JJY, Lin JK. Curcumin induces apoptosis in immortalized NIH 3 T3 and malignant cancer cell lines. Nutr Cancer. 1996;26(1):111–20.PubMedCrossRefGoogle Scholar
  75. 75.
    Watson JL, Hill R, Yaffe PB, Greenshields A, Walsh M, Lee PW, et al. Curcumin causes superoxide anion production and p53-independent apoptosis in human colon cancer cells. Cancer Lett. 2010;297(1):1–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Kohno M, Pouyssegur J. Targeting the ERK signaling pathway in cancer therapy. Ann Med. 2006;38(3):200–11.PubMedCrossRefGoogle Scholar
  77. 77.
    Adjei AA. Blocking oncogenic ras signaling for cancer therapy. J Natl Cancer Inst. 2001;93(14):1062–74.PubMedCrossRefGoogle Scholar
  78. 78.
    Cao AL, Tang QF, Zhou WC, Qiu YY, Hu SJ, Yin PH. Ras/ERK signaling pathway is involved in curcumin-induced cell cycle arrest and apoptosis in human gastric carcinoma AGS cells. J Asian Nat Prod Res. 2015;17(1):56–63.PubMedCrossRefGoogle Scholar
  79. 79.
    Ono M, Higuchi T, Takeshima M, Chen C, Nakano S. Differential anti-tumor activities of curcumin against ras-and src-activated human adenocarcinoma cells. Biochem Biophys Res Commun. 2013;436(2):186–91.PubMedCrossRefGoogle Scholar
  80. 80.
    Kim M-S, Kang H-J, Moon A. Inhibition of invasion and induction of apoptosis by curcumin in H-ras-transformed MCF10A human breast epithelial cells. Arch Pharm Res. 2001;24(4):349–54.PubMedCrossRefGoogle Scholar
  81. 81.
    Limtrakul PN, Anuchapreeda S, Lipigorngoson S, Dunn FW. Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin. BMC Cancer. 2001;1(1):1.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Vara JÁF, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004;30(2):193–204.CrossRefGoogle Scholar
  83. 83.
    Wyatt LA, Filbin MT, Keirstead HS. PTEN inhibition enhances neurite outgrowth in human embryonic stem cell–derived neuronal progenitor cells. J Comp Neurol. 2014;522(12):2741–55.PubMedCrossRefGoogle Scholar
  84. 84.
    Polivka J, Janku F. Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther. 2014;142(2):164–75.PubMedCrossRefGoogle Scholar
  85. 85.
    Qiao Q, Jiang Y, Li G. Inhibition of the PI3K/AKT-NF-κB pathway with curcumin enhanced radiation-induced apoptosis in human Burkitt’s lymphoma. J Pharmacol Sci. 2013;121(4):247–56.PubMedCrossRefGoogle Scholar
  86. 86.
    Yu S, Shen G, Khor TO, Kim J-H, Kong A-NT. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Mol Cancer Ther. 2008;7(9):2609–20.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Akkoç Y, Berrak Ö, Arısan ED, Obakan P, Çoker-Gürkan A, Palavan-Ünsal N. Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl-2 through activation of autophagy in MCF-7 cells. Biochem Pharmacol. 2015;71:161–71.Google Scholar
  88. 88.
    Polakis P. Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 2012;4(5):a008052.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Morin PJ. β-catenin signaling and cancer. BioEssays. 1999;21(12):1021–30.PubMedCrossRefGoogle Scholar
  90. 90.
    Kim HJ, Park SY, Park OJ, Kim YM. Curcumin suppresses migration and proliferation of Hep3B hepatocarcinoma cells through inhibition of the Wnt signaling pathway. Mol Med Rep. 2013;8(1):282–6.PubMedGoogle Scholar
  91. 91.
    Leow P-C, Bahety P, Boon CP, Lee CY, Tan KL, Yang T, et al. Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway. Eur J Med Chem. 2014;71:67–80.PubMedCrossRefGoogle Scholar
  92. 92.
    Kolb TM, Davis MA. The tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) provokes a prolonged morphologic response and ERK activation in Tsc2-null renal tumor cells. Toxicol Sci. 2004;81(1):233–42.PubMedCrossRefGoogle Scholar
  93. 93.
    Libermann TA, Zerbini LF. Targeting transcription factors for cancer gene therapy. Curr Gene Ther. 2006;6(1):17–33.PubMedCrossRefGoogle Scholar
  94. 94.
    Dolcet X, Llobet D, Pallares J, Matias-Guiu X. NF-kB in development and progression of human cancer. Virchows Arch. 2005;446(5):475–82.PubMedCrossRefGoogle Scholar
  95. 95.
    Mishra A, Kumar R, Tyagi A, Kohaar I, Hedau S, Bharti AC et al. Curcumin modulates cellular AP-1, NF-kB, and HPV16 E6 proteins in oral cancer. ecancermedicalscience. 2015;9.Google Scholar
  96. 96.
    Singh S, Aggarwal BB. Activation of transcription factor NF-κB is suppressed by curcumin (diferuloylmethane). J Biol Chem. 1995;270(42):24995–5000.PubMedCrossRefGoogle Scholar
  97. 97.
    Marín YE, Wall BA, Wang S, Namkoong J, Martino JJ, Suh J, et al. Curcumin downregulates the constitutive activity of NF-κB and induces apoptosis in novel mouse melanoma cells. Melanoma Res. 2007;17(5):274–83.PubMedCrossRefGoogle Scholar
  98. 98.
    Marquardt JU, Gomez-Quiroz L, Camacho LOA, Pinna F, Lee Y-H, Kitade M, et al. Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer. J Hepatol. 2015;63(3):661–9.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Furqan M, Akinleye A, Mukhi N, Mittal V, Chen Y, Liu D. STAT inhibitors for cancer therapy. J Hematol Oncol. 2013;6(1):1–11.CrossRefGoogle Scholar
  100. 100.
    Lavecchia A, Di Giovanni C, Novellino E. STAT-3 inhibitors: state of the art and new horizons for cancer treatment. Curr Med Chem. 2011;18(16):2359–75.PubMedCrossRefGoogle Scholar
  101. 101.
    Yu H, Jove R. The STATs of cancer—new molecular targets come of age. Nat Rev Cancer. 2004;4(2):97–105.PubMedCrossRefGoogle Scholar
  102. 102.
    Blasius R, Reuter S, Henry E, Dicato M, Diederich M. Curcumin regulates signal transducer and activator of transcription (STAT) expression in K562 cells. Biochem Pharmacol. 2006;72(11):1547–54.PubMedCrossRefGoogle Scholar
  103. 103.
    Saydmohammed M, Joseph D, Syed V. Curcumin suppresses constitutive activation of STAT-3 by up-regulating protein inhibitor of activated STAT-3 (PIAS-3) in ovarian and endometrial cancer cells. J Cell Biochem. 2010;110(2):447–56.PubMedGoogle Scholar
  104. 104.
    Aggarwal BB, Surh Y-J, Shishodia, S. The molecular targets and therapeutic uses of curcumin in health and disease. Springer Science & Business Media; 2007.Google Scholar
  105. 105.
    Ferreira LC, Arbab AS, Jardim-Perassi BV, Borin TF, Gonçalves NN, Nadimpalli RSV, et al. Abstract A02: effect of curcumin on the tumor growth and angiogenesis of breast cancer. Cancer Res. 2015;75(1 Supplement):A02-A.CrossRefGoogle Scholar
  106. 106.
    Chakraborty G, Jain S, Kale S, Raja R, Kumar S, Mishra R, et al. Curcumin suppresses breast tumor angiogenesis by abrogating osteopontin-induced VEGF expression. Mol Med Rep. 2008;1(5):641–6.PubMedGoogle Scholar
  107. 107.
    Yoysungnoen P, Wirachwong P, Changtam C, Suksamrarn A, Patumraj S. Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice. World J Gastroenterol. 2008;14(13):2003.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Arbiser JL, Klauber N, Rohan R, van Leeuwen R, Huang M-T, Fisher C, et al. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med. 1998;4(6):376.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Arbiser J. Antiangiogenic therapy and dermatology: a review. Med Actual. 1997;33(10):687–96.Google Scholar
  110. 110.
    Steeg PS. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006;12(8):895–904.PubMedCrossRefGoogle Scholar
  111. 111.
    Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011;147(2):275–92.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Woo MS, Jung SH, Kim SY, Hyun JW, Ko KH, Kim WK, et al. Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells. Biochem Biophys Res Commun. 2005;335(4):1017–25.PubMedCrossRefGoogle Scholar
  113. 113.
    Radhakrishnan VM, Kojs P, Young G, Ramalingam R, Jagadish B, Mash EA, et al. pTyr 421 cortactin is overexpressed in colon cancer and is dephosphorylated by curcumin: involvement of non-receptor type 1 protein tyrosine phosphatase (PTPN1). PLoS One. 2014;9(1):e85796.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Killian PH, Kronski E, Michalik KM, Barbieri O, Astigiano S, Sommerhoff CP, et al. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and-2. Carcinogenesis. 2012;33(12):2507–19.PubMedCrossRefGoogle Scholar

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© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Pandima Devi Kasi
    • 1
  • Rajavel Tamilselvam
    • 1
  • Krystyna Skalicka-Woźniak
    • 2
  • Seyed Fazel Nabavi
    • 3
  • Maria Daglia
    • 4
  • Anupam Bishayee
    • 5
  • Hamidreza Pazoki-toroudi
    • 6
  • Seyed Mohammad Nabavi
    • 3
  1. 1.Department of BiotechnologyAlagappa University (Science Campus)KaraikudiIndia
  2. 2.Department of Pharmacognosy with Medicinal Plants UnitMedical University of LublinLublinPoland
  3. 3.Applied Biotechnology Research CenterBaqiyatallah University of Medical SciencesTehranIran
  4. 4.Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology SectionUniversity of PaviaPaviaItaly
  5. 5.Department of Pharmaceutical Sciences, College of PharmacyLarkin Health Sciences InstituteMiamiUSA
  6. 6.Physiology Research Center, Faculty of MedicineIran University of Medical SciencesTehranIran

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