Curcumin: Its Role in Regulation of HIF-1α in Gastric Cancer

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Role of Transcription Factors in Gastrointestinal Malignancies
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Abstract

Gastric cancer is a malignancy and is the fourth most common cause of cancer globally. An oxygen-deficient microenvironment is a common state of gastric cancer, associated with tumor invasion and metastasis. Under hypoxic conditions, cancer cells start their own adaptive pathways to have a facilitated oxygen and energy supply for survival. In this condition, hypoxia-inducible factors (HIF) such as HIF-1α have a vital role particularly in cellular response to hypoxia and stimulate the major hallmark processes of tumor development, for example, angiogenesis, glucose transport, and metabolism by activating the transcriptional factors of various targeted gene involved in tumor development. Curcumin, a major phytochemical extracted from roots of Curcuma longa, inhibits proliferation of many types of solid cancer cells. Earlier, curcumin shows strong therapeutic potential against gastric cancer cell lines by downregulating the levels of the oncogene c-Myc expression and thereby hindering the expression of the targeted gene. Curcumin also exhibits antitumor effects under hypoxic conditions by significantly decreasing levels of hypoxia-induced HIF-1α protein, in cancer cells. Furthermore, curcumin eliminates cell proliferation, migration, and invasiveness generated by a hypoxic microenvironment and associated with HIF-1α accumulation.

The original version of this chapter was revised. The book was inadvertently published without Abstracts and Keywords, which are now included in all the chapters. An erratum to this chapter can be found at https://doi.org/10.1007/978-981-10-6728-0_39

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References

  1. Abreu MT, Peek RM Jr (2014) Gastrointestinal malignancy and the microbiome. Gastroenterology 146:1534–1546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 23:363–398

    PubMed  CAS  Google Scholar 

  3. Amanda MG, Robert AO (2008) Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes. Nutr Metab 12:1–13

    Google Scholar 

  4. Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, Tharakan ST, Misra K, Priyadarsini IK, Rajasekharan KN, Aggarwal BB (2008a) Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Phramacol 76(11):1590–1611

    Article  CAS  Google Scholar 

  5. Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, Tharakan ST, Misra K, Priyadarsini KI, Rajasekharan KN, Aggarwal BB (2008b) Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol 76:1590–1611

    Article  CAS  Google Scholar 

  6. Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB (2002) Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of bcl-2 and bcl-xl. Carcinogenesis 23:143–150

    Article  CAS  PubMed  Google Scholar 

  7. Arceci RJ (1996) Tumor cell survival and resistance to therapy. Curr Opin Hematol 3:279–287

    Article  CAS  PubMed  Google Scholar 

  8. Chen HW, Lee JY, Huang JY, Wang CC, Chen WJ, Su SF, Huang CW, Ho CC, Chen JJ, Tsai MF, Yu SL, Yang PC (2008) Curcumin inhibits lung cancer cell invasion and metastasis through the tumor suppressor HLJ1. Cancer Res 18:7428–7438

    Article  Google Scholar 

  9. Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii-Kuriyama Y (1997) A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1α regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl AcadSci USA 94:4273–4278

    Article  CAS  Google Scholar 

  10. Ferlay J, Soerjomatara I, Dikshit R, Eser S, Mathers C, Rebelo M et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN. Int J Cancer 136(5):E359–E386

    Google Scholar 

  11. Giles RH, van Es JH, Clevers H (2003) Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 1653(1):1–24

    Article  CAS  Google Scholar 

  12. Han SS, Chung ST, Robertson DA, Ranjan D, 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(2):152–161

    Article  CAS  PubMed  Google Scholar 

  13. Kang Y, Hu W, Bai E, Zheng H, Liu Z, Wu J, ** R, Zhao C, Liang G (2016) Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway. Onco Targets and Terapy 9:7373–7384

    Article  CAS  Google Scholar 

  14. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F (2014) Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomark Prev 23:700–713

    Article  Google Scholar 

  15. Kim DC, Park KR, Jeong YJ et al (2016) Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells. Oncol Lett 11(2):991–997

    Article  CAS  PubMed  Google Scholar 

  16. Kolev TM, Velcheva EA, Stamboliyska BA, Spiteller M (2005) DFT and experimental studies of the structure and vibrational spectra of curcumin. Int J Quantum Chem 102:1069–1079

    Article  CAS  Google Scholar 

  17. Krishnamachary B, Berg-Dixon S, Kelly B, Agani F, Feldser D, Ferreira G, Iyer N, LaRusch J, Pak B, Taghavi P, Semenza GL (2003) Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res 63:1138–1143

    CAS  Google Scholar 

  18. Liu X, Sun K, Song A, Zhang X, Zhang X, He X (2014) Curcumin inhibits proliferation of gastric cancer cells by impairing ATP-sensitive potassium channel opening. World J Surg Oncol 12:389

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lu X, Kang Y (2010) Hypoxia and hypoxia-inducible factors (HIFs): master regulators of metastasis. Clin Cancer Res 16:5928–5935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Majmundar AJ, Wong WJ, Simon MC (2010) Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 40:294–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mukhopadhyay A, Banerjee S, Stafford LJ, **a C, Liu M, Aggarwal BB (2002) Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation. Oncogene 21(57):8852–8861

    Article  CAS  PubMed  Google Scholar 

  22. Prasad NS, Sarasija S (1997) Spectrophotometric estimation of curcumin. Indian Drugs 34:227–228

    Google Scholar 

  23. Rajalingam K, Schreck R, Rapp UR, Albert S (2007) Ras oncogenes and their downstream targets. Biochimica et Biophysica Acta 1773(8):1177–1195

    Article  CAS  PubMed  Google Scholar 

  24. Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL, Bedi A (2000) Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 14:34–44

    PubMed  PubMed Central  CAS  Google Scholar 

  25. Rohwer N, Cramer T (2010) HIFs as central regulators of gastric cancer pathogenesis. Cancer Biol Ther 10:383–385

    Article  CAS  PubMed  Google Scholar 

  26. Salem M, Rohani S, Gillies ER (2014) Curcumin, a promising anti-cancer therapeutic: a review of its chemical properties, bioactivity and approaches to cancer cell delivery. RSC Adv 108:15–29

    Google Scholar 

  27. Shishodia S, Amin HM, Lai R, Aggarwal BB (2005) Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem Pharmacol 70(5):700–713

    Article  CAS  PubMed  Google Scholar 

  28. Simon A, Allais DP, Duroux JL, Basly JP, Durand-Fontanier S, Delage C (1998) Inhibitory effect of curcuminoids on MCF-7 cell proliferation and structure-activity relationships. Cancer Lett 129(1):111–116

    Article  CAS  PubMed  Google Scholar 

  29. Singh M, Singh N (2009) Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells. Mol Cell Biochem 325:107–119

    Article  CAS  PubMed  Google Scholar 

  30. Tang XQ, Bi H, Feng JQ, Cao JG (2005) Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR. Acta Pharmacol Sin 26:1009–1016

    Article  CAS  PubMed  Google Scholar 

  31. Wang GL, Jiang BH, Rue EA, Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 92:5510–5514

    Article  CAS  PubMed  Google Scholar 

  32. Wang Y, Li Z, Zhang H, ** H, Sun L et al (2010) HIF-1α and HIF-2α correlate with migration and invasion in gastric cancer. Cancer Biol Ther 10(4):376–382

    Article  CAS  PubMed  Google Scholar 

  33. Xu MX, Zhao L, Deng C et al (2013) Curcumin suppresses proliferation and induces apoptosis of human hepatocellular carcinoma cells via the wnt signaling pathway. Int J Oncol 43:1951–1959

    Article  CAS  PubMed  Google Scholar 

  34. Zheng R, Deng Q, Liu Y, Zhao P (2017) Curcumin inhibits gastric carcinoma cell growth and induces apoptosis by suppressing the Wnt/β - catenin signaling pathway. Med Sci Monit: Int Med J Exp Clin Res 23:163–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Tapan K. Barik .

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Barik, T.K., Swain, S.N. (2017). Curcumin: Its Role in Regulation of HIF-1α in Gastric Cancer. In: Nagaraju, G., Bramhachari, P. (eds) Role of Transcription Factors in Gastrointestinal Malignancies. Springer, Singapore. https://doi.org/10.1007/978-981-10-6728-0_14

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