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Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer cells

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Tumor Biology

Abstract

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component in hot peppers. The role of capsaicin in carcinogenesis is quite controversial. Although some investigators suspect that capsaicin is a carcinogen, co-carcinogen, or tumor promoter, others have reported that it has chemopreventive and chemotherapeutic effects. The present study aimed to evaluate the cytotoxicity and chemosensitizing activities of capsaicin alone and on 5-flourouracil (5-FU)-treated gastric cancer cells. In this study, the gastric cancer cell line HGC-27 was used and capsaicin used as a chemosensitizer and 5-flourouracil (5-FU) was used as chemotherapeutic. Cytotoxicity and chemosensitizing activities were analyzed with MTT assay; supernatant levels of LDH and glucose were detected as biochemical markers of cell viability; cytochrome c and AIF were evaluated with western blot; and additionally, wound-healing assays were employed. Results suggested that capsaicin had significant anticancer abilities; such capsaicin were capable of causing multifold decreases in the half maximal inhibitory concentration IC50 value of 5-FU. The continuing controversy surrounding consumption or topical application of capsaicin clearly suggests that more well-controlled epidemiologic studies are needed to evaluate the safety and efficacy of capsaicin use. In summary, the present study demonstrated that capsaicin has the potential to be used for treating gastric carcinoma with 5-FU in vitro.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Zheng Z, He X, Li J, Yu B, Chen X, Ji J, et al. RhoGDI2 confers resistance to 5-fluorouracil in human gastric cancer cells. Oncol Lett. 2013;5:255–60.

    PubMed Central  CAS  PubMed  Google Scholar 

  3. Moon JY, Cho M, Ahn KS, Cho SK. Nobiletin induces apoptosis and potentiates the effects of the anticancer drug 5-fluorouracil in p53-mutated SNU-16 human gastric cancer cells. Nutr Cancer. 2013;65(2):286–95.

    Article  CAS  PubMed  Google Scholar 

  4. Yadav VR, Prasad S, Sung B, Kannappan R, Aggarwal BB. Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer. Toxins (Basel). 2010;2(10):2428–66.

    Article  CAS  Google Scholar 

  5. Díaz-Laviada I. Effect of capsaicin on prostate cancer cells. Future Oncol. 2010;6(10):1545–50.

    Article  PubMed  Google Scholar 

  6. Bode AM, Dong Z. The two faces of capsaicin. Cancer Res. 2011;71:2809–14.

    Article  CAS  PubMed  Google Scholar 

  7. Liao F, Yang Z, Lu X, Guo X, Dong W. Sinomenine sensitizes gastric cancer cells to 5-fluorouracil in vitro and in vivo. Oncol Lett. 2013;6:1604–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  8. Zhang N, Yin Y, Xu S, Chen W. 5-Fluorouracil: mechanisms of resistance and reversal strategies. Molecules. 2008;13:1551–69.

    Article  CAS  PubMed  Google Scholar 

  9. Arias JL. Novel strategies to improve the anticancer action of 5-fluorouracil by using drug delivery systems. Molecules. 2008;13:2340–69.

    Article  CAS  PubMed  Google Scholar 

  10. Gubta SC, Kannappan R, Reuter S, Kim JH, Aggarwal BB. Chemosensitization of tumors by resveratrol. Ann NY Acad Sci. 2011;1215:150–60.

    Article  Google Scholar 

  11. WHO. Global cancer rates could increase by 50 % to 15 million by 2020. 2014. http://www.who.int/mediacentre/news/releases/2003/pr27/en Accessed 14 Jan 2014.

  12. Yang KM, Pyo JO, Kim GY, Yu R, Han IS, Ju SA, et al. Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines. Cell Mol Biol Lett. 2009;14:497–510.

    Article  CAS  PubMed  Google Scholar 

  13. Huang SP, Chen JC, Wu CC, Chen CT, Tang NY, Ho YT, et al. Capsaicin-induced apoptosis in human hepatoma HepG2 cells. Anticancer Res. 2009;29:165–74.

    CAS  PubMed  Google Scholar 

  14. Sanchez AM, Sanchez MG, Malagarie-Cazenave S, Olea N, Diaz-Laviada I. Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis. 2006;11:89–99.

    Article  CAS  PubMed  Google Scholar 

  15. Surh YJ, Lee SS. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen? Food Chem Toxicol. 1996;34:313–6.

    Article  CAS  PubMed  Google Scholar 

  16. Surh YJ, Lee SS. Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential. Life Sci. 1995;56:1845–55.

    Article  CAS  PubMed  Google Scholar 

  17. Oyagbemi AA, Saba AB, Azeez OI. Capsaicin: a novel chemopreventive molecule and its underlying molecular mechanisms of action. Indian J Cancer. 2010;47:53–8.

    Article  CAS  PubMed  Google Scholar 

  18. Ito K, Nakazato T, Yamato K, Miyakawa Y, Yamada T, Hozumi N, et al. Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Cancer Res. 2004;64:1071–8.

    Article  CAS  PubMed  Google Scholar 

  19. Amantini C, Mosca M, Nabissi M, Lucciarini R, Caprodossi S, Arcella A, et al. Capsaicin-induced apoptosis of glioma cells is mediated by TRPV1 vanilloid receptor and requires p38 MAPK activation. J Neurochem. 2007;102:977–90.

    Article  CAS  PubMed  Google Scholar 

  20. Kim MY, Trudel LJ, Wogan GN. Apoptosis induced by capsaicin and resveratrol in colon carcinoma cells requires nitric oxide production and caspase activation. Anticancer Res. 2009;29:3733–40.

    CAS  PubMed  Google Scholar 

  21. Gupta SC, Kim JH, Prasad S, Aggarwal BB. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev. 2010;29:405–34.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Sung B, Prasad S, Yadav VR, Aggarwal BB. Cancer cell signaling pathways targeted by spice-derived nutraceuticals. Nutr Cancer. 2012;64(2):173–97.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Gupta SC, Kismali G, Aggarwal BB. Curcumin, a component of turmeric: from farm to pharmacy. Biofactors. 2013;39(1):2–13.

    Article  CAS  PubMed  Google Scholar 

  24. Chaturvedi MM, Sung B, Yadav VR, Kannappan R, Aggarwal BB. NF-κB addiction and its role in cancer: ‘one size does not fit all’. Oncogene. 2011;30:1615–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Sethi G, Sung B, Aggarwal BB. Nuclear factor-kappaB activation: from bench to bedside. Exp Biol Med (Maywood). 2008;233:21–31.

    Article  CAS  Google Scholar 

  26. Bitencourt S, Mesquita F, Basso B, Schmid J, Ferreira G, Rizzo L, et al. Capsaicin modulates proliferation, migration, and activation of hepatic stellate cells. Cell Biochem Biophys. 2014;68(2):387–96.

    Google Scholar 

  27. Shin DH, Kim OH, Jun HS, Kang MK. Inhibitory effect of capsaicin on B16-F10 melanoma cell migration via the phosphatidylinositol 3-kinase/Akt/Rac1 signal pathway. Exp Mol Med. 2008;40(5):486–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Liu NC, Hsieh PF, Hsieh MK, Zeng ZM, Cheng HL, Liao JW, et al. Capsaicin-mediated tNOX (ENOX2) up-regulation enhances cell proliferation and migration in vitro and in vivo. J Agric Food Chem. 2012;60(10):2758–65.

    Article  CAS  PubMed  Google Scholar 

  29. Yang J, Li TZ, Xu GH, Luo BB, Chen YX, Zhang T. Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways. Neoplasma. 2013;60(4):364–72.

    Article  CAS  PubMed  Google Scholar 

  30. Sellers WR, Fisher DE. Apoptosis and cancer drug targeting. J Clin Invest. 1999;104:1655–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer. 1972;26:239–57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Hu XZ, Xu Y, Hu DC, Hui Y, Yang FX. Apoptosis induction on human hepatoma cells Hep G2 of decabrominated diphenyl ether (PBDE-209). Toxicol Lett. 2007;171:19–28.

    Article  CAS  PubMed  Google Scholar 

  33. Cande C, Vahsen N, Garrido C, Kroemer G. Apoptosis-inducing factor (AIF): caspase-independent after all. Cell Death Differ. 2004;11:591–5.

    CAS  PubMed  Google Scholar 

  34. Ow YP, Green DR, Hao Z, Mak TW. Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol. 2008;9:532–42.

    Article  CAS  PubMed  Google Scholar 

  35. Serra I, Yamamoto M, Calvo A, Cavada G, Baez S, Endoh K, et al. Association of chili pepper consumption, low socioeconomic status and longstanding gallstones with gallbladder cancer in a Chilean population. Int J Cancer. 2002;102:407–11.

    Article  CAS  PubMed  Google Scholar 

  36. Lopez-Carrillo L, Hernandez Avila M, Dubrow R. Chili pepper consumption and gastric cancer in Mexico: a case-control study. Am J Epidemiol. 1994;139:263–71.

    CAS  PubMed  Google Scholar 

  37. Notani PN, Jayant K. Role of diet in upper aerodigestive tract cancers. Nutr Cancer. 1987;10:103–13.

    Article  CAS  PubMed  Google Scholar 

  38. Buiatti E, Palli D, Decarli A, Amadori D, Avellini C, Bianchi S, et al. A case-control study of gastric cancer and diet in Italy. Int J Cancer. 1989;44:611–6.

    Article  CAS  PubMed  Google Scholar 

  39. Chuang YC, Yoshimura N, Huang CC, Wu M, Chiang PH, Chancellor MB. Intraprostatic botulinum toxin a injection inhibits cyclooxygenase-2 expression and suppresses prostatic pain on capsaicin induced prostatitis model in rat. J Urol. 2008;180(2):742–8.

    Article  CAS  PubMed  Google Scholar 

  40. Bommareddy A, Eggleston W, Prelewicz S, Antal A, Witczak Z, McCune DF, et al. Chemoprevention of prostate cancer by major dietary phytochemicals. Anticancer Res. 2013;33(10):4163–74.

    CAS  PubMed  Google Scholar 

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Acknowledgments

Authors sincerely thank Dr. Begum Yurdakok from the Department of Pharmacology, Ankara University.

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Authors and Affiliations

  1. Faculty of Veterinary Medicine, Department of Biochemistry, Ankara University, Ankara, 06110, Turkey

    Ogunc Meral, Merve Alpay, Gorkem Kismali, Mert Pekcan & Tevhide Sel

  2. Celal Bayar University, Manisa, Turkey

    Funda Kosova

  3. Faculty of Medicine, Department of Biochemistry, Canakkale Onsekiz Mart University, Canakkale, Turkey

    Dilek Ulker Cakir

  4. Faculty of Medicine, Duzce University, Duzce, Turkey

    Merve Alpay

  5. Faculty of Medicine, Department of Medical Biology, Gaziosmanpasa University, Tokat, Turkey

    Serbulent Yigit

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  1. Ogunc Meral
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Correspondence to Ogunc Meral.

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Meral, O., Alpay, M., Kismali, G. et al. Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer cells. Tumor Biol. 35, 6485–6492 (2014). https://doi.org/10.1007/s13277-014-1864-6

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  • DOI: https://doi.org/10.1007/s13277-014-1864-6

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