Tumor Biology

, Volume 35, Issue 7, pp 6485–6492 | Cite as

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

  • Ogunc Meral
  • Merve Alpay
  • Gorkem Kismali
  • Funda Kosova
  • Dilek Ulker Cakir
  • Mert Pekcan
  • Serbulent Yigit
  • Tevhide Sel
Research Article


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.


Capsaicin 5-Fluorouracil Gastric cancer Cytochrome c 



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

Conflicts of interest



  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 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.PubMedCentralPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 5.
    Díaz-Laviada I. Effect of capsaicin on prostate cancer cells. Future Oncol. 2010;6(10):1545–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Bode AM, Dong Z. The two faces of capsaicin. Cancer Res. 2011;71:2809–14.CrossRefPubMedGoogle Scholar
  7. 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.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Zhang N, Yin Y, Xu S, Chen W. 5-Fluorouracil: mechanisms of resistance and reversal strategies. Molecules. 2008;13:1551–69.CrossRefPubMedGoogle Scholar
  9. 9.
    Arias JL. Novel strategies to improve the anticancer action of 5-fluorouracil by using drug delivery systems. Molecules. 2008;13:2340–69.CrossRefPubMedGoogle Scholar
  10. 10.
    Gubta SC, Kannappan R, Reuter S, Kim JH, Aggarwal BB. Chemosensitization of tumors by resveratrol. Ann NY Acad Sci. 2011;1215:150–60.CrossRefGoogle Scholar
  11. 11.
    WHO. Global cancer rates could increase by 50 % to 15 million by 2020. 2014. Accessed 14 Jan 2014.
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 15.
    Surh YJ, Lee SS. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen? Food Chem Toxicol. 1996;34:313–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Surh YJ, Lee SS. Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential. Life Sci. 1995;56:1845–55.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.PubMedGoogle Scholar
  21. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  22. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Gupta SC, Kismali G, Aggarwal BB. Curcumin, a component of turmeric: from farm to pharmacy. Biofactors. 2013;39(1):2–13.CrossRefPubMedGoogle Scholar
  24. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Sethi G, Sung B, Aggarwal BB. Nuclear factor-kappaB activation: from bench to bedside. Exp Biol Med (Maywood). 2008;233:21–31.CrossRefGoogle Scholar
  26. 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. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 30.
    Sellers WR, Fisher DE. Apoptosis and cancer drug targeting. J Clin Invest. 1999;104:1655–61.PubMedCentralCrossRefPubMedGoogle Scholar
  31. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 33.
    Cande C, Vahsen N, Garrido C, Kroemer G. Apoptosis-inducing factor (AIF): caspase-independent after all. Cell Death Differ. 2004;11:591–5.PubMedGoogle Scholar
  34. 34.
    Ow YP, Green DR, Hao Z, Mak TW. Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol. 2008;9:532–42.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 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.PubMedGoogle Scholar
  37. 37.
    Notani PN, Jayant K. Role of diet in upper aerodigestive tract cancers. Nutr Cancer. 1987;10:103–13.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefPubMedGoogle Scholar
  39. 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.CrossRefPubMedGoogle Scholar
  40. 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.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ogunc Meral
    • 1
  • Merve Alpay
    • 1
    • 4
  • Gorkem Kismali
    • 1
  • Funda Kosova
    • 2
  • Dilek Ulker Cakir
    • 3
  • Mert Pekcan
    • 1
  • Serbulent Yigit
    • 5
  • Tevhide Sel
    • 1
  1. 1.Faculty of Veterinary Medicine, Department of BiochemistryAnkara UniversityAnkaraTurkey
  2. 2.Celal Bayar UniversityManisaTurkey
  3. 3.Faculty of Medicine, Department of BiochemistryCanakkale Onsekiz Mart UniversityCanakkaleTurkey
  4. 4.Faculty of MedicineDuzce UniversityDuzceTurkey
  5. 5.Faculty of Medicine, Department of Medical BiologyGaziosmanpasa UniversityTokatTurkey

Personalised recommendations