Role of Capsaicin in Cancer Prevention

Part of the Diet and Cancer book series (DICA, volume 3)


One of the aims of current cancer prevention research is to find non-toxic agents that can prevent and /or suppress the growth of cancer cells. In this regard, capsaicin, a main constituent of hot chili peppers, has garnered a great deal of attention as a chemo-preventive agent against cancer. In this book chapter capsaicin is discussed as a potent anti-cancer agent in different models, including pancreatic, prostate, lung, breast, colon, brain, hepatic, bladder, skin and stomach cancers. Investigators have shown that the anti-cancer effect of capsaicin results from modulation of key signaling molecules in major signaling pathways such as stress, cell cycle, mitochondrial dysfunction and ER-stress. Furthermore, capsaicin has proven effective in vivo in the animal models of various types of cancer. Overall findings on capsaicin suggest that capsaicin is a promising agent for the treatment of various types of cancer that nonetheless requires further clinical studies. This chapter focuses on the chemo-preventive efficacy of capsaicin in various types of cancer models.


Capsaicin Chili peppers Cancer Apoptosis Stress signal Mitochondria In vitro and in vivo 


  1. Aggarwal BB, Shishodia S (2006) Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 71:1397–1421PubMedCrossRefGoogle Scholar
  2. Akiba Y, Kato S, Katsube K, Nakamura M, Takeuchi K, Ishii H, Hibi T (2004) Transient receptor potential vanilloid subfamily 1 expressed in pancreatic islet beta cells modulates insulin secretion in rats. Biochem Biophys Res Commun 321:219–225PubMedCrossRefGoogle Scholar
  3. Alves RC, Alves D, Guz B, Matos C, Viana M, Harriz M, Terrabuio D, Kondo M, Gampel O, Polletti P (2011) Advanced hepatocellular carcinoma. Review of targeted molecular drugs. Ann Hepatol Off J Mex Assoc Hepatol 10:21–27Google Scholar
  4. Amantini C, Mosca M, Nabissi M, Lucciarini R, Caprodossi S, Arcella A, Giangaspero F, Santoni G (2007) Capsaicin-induced apoptosis of glioma cells is mediated by TRPV1 vanilloid receptor and requires p38 MAPK activation. J Neurochem 102:977–990PubMedCrossRefGoogle Scholar
  5. Amantini C, Ballarini P, Caprodossi S, Nabissi M, Morelli MB, Lucciarini R, Cardarelli MA, Mammana G, Santoni G (2009) Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. Carcinogenesis 30:1320–1329PubMedCrossRefGoogle Scholar
  6. Anandakumar P, Jagan S, Kamaraj S, Ramakrishnan G, Titto AA, Devaki T (2008a) Beneficial influence of capsaicin on lipid peroxidation, membrane-bound enzymes and glycoprotein profile during experimental lung carcinogenesis. J Pharm Pharmacol 60:803–808PubMedCrossRefGoogle Scholar
  7. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Vinodhkumar R, Devaki T (2008b) Capsaicin modulates pulmonary antioxidant defense system during benzo(a)pyrene-induced lung cancer in Swiss albino mice. Phytother Res 22:529–533PubMedCrossRefGoogle Scholar
  8. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Vinodhkumar R, Devaki T (2008c) Stabilization of pulmonary mitochondrial enzyme system by capsaicin during benzo(a)pyrene induced experimental lung cancer. Biomed Pharmacother 62:390–394PubMedCrossRefGoogle Scholar
  9. Anandakumar P, Jagan S, Kamaraj S, Ramakrishnan G, Clara JB, Pathitha D, Kavitha T, Devaki T (2009a) Ameliorating effect of capsaicin on alterations in lipid metabolism during mice lung carcinoma. Arch Pharmacal Res 32:229–234CrossRefGoogle Scholar
  10. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Devaki T (2009b) Lysosomal abnormalities during benzo(a)pyrene-induced experimental lung carcinogenesis–defensive role of capsaicin. Fundam Clin Pharmacol 23:97–103PubMedCrossRefGoogle Scholar
  11. Anandakumar P, Kamaraj S, Ramakrishnan G, Jagan S, Devaki T (2009c) Chemopreventive task of capsaicin against benzo(a)pyrene-induced lung cancer in Swiss albino mice. Basic Clin Pharmacol Toxicol 104:360–365PubMedCrossRefGoogle Scholar
  12. Baek YM, Hwang HJ, Kim SW, Hwang HS, Lee SH, Kim JA, Yun JW (2008) A comparative proteomic analysis for capsaicin-induced apoptosis between human hepatocarcinoma (HepG2) and human neuroblastoma (SK-N-SH) cells. Proteomics 8:4748–4767PubMedCrossRefGoogle Scholar
  13. Bai H, Li H, Zhang W, Matkowskyj KA, Liao J, Srivastava SK, Yang GY (2011) Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice. Carcinogenesis 32:1689–1696PubMedCrossRefGoogle Scholar
  14. Bhutani M, Pathak AK, Nair AS, Kunnumakkara AB, Guha S, Sethi G, Aggarwal BB (2007) Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation. Clin Cancer Res Off J Am Assoc Cancer Res 13:3024–3032CrossRefGoogle Scholar
  15. Block G, Patterson B, Subar A (1992) Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer 18:1–29PubMedCrossRefGoogle Scholar
  16. Brown KC, Witte TR, Hardman WE, Luo H, Chen YC, Carpenter AB, Lau JK, Dasgupta P (2010) Capsaicin displays anti-proliferative activity against human small cell lung cancer in cell culture and nude mice models via the E2F pathway. PLoS One 5:e10243PubMedCrossRefGoogle Scholar
  17. Chang HC, Chen ST, Chien SY, Kuo SJ, Tsai HT, Chen DR (2011) Capsaicin may induce breast cancer cell death through apoptosis-inducing factor involving mitochondrial dysfunction. Hum Exp Toxicol 30:1657–1665PubMedCrossRefGoogle Scholar
  18. Choi CH, Jung YK, Oh SH (2010) Autophagy induction by capsaicin in malignant human breast cells is modulated by p38 and extracellular signal-regulated mitogen-activated protein kinases and retards cell death by suppressing endoplasmic reticulum stress-mediated apoptosis. Mol Pharmacol 78:114–125PubMedCrossRefGoogle Scholar
  19. Chou CC, Wu YC, Wang YF, Chou MJ, Kuo SJ, Chen DR (2009) Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway. Oncol Rep 21:665–671PubMedGoogle Scholar
  20. Chow J, Norng M, Zhang J, Chai J (2007) TRPV6 mediates capsaicin-induced apoptosis in gastric cancer cells – mechanisms behind a possible new “hot” cancer treatment. Biochim Biophys Acta 1773:565–576PubMedCrossRefGoogle Scholar
  21. El-Serag HB (2011) Hepatocellular carcinoma. N Engl J Med 365:1118–1127PubMedCrossRefGoogle Scholar
  22. Ferguson LR (1994) Antimutagens as cancer chemopreventive agents in the diet. Mutat Res 307:395–410PubMedCrossRefGoogle Scholar
  23. Gil YG, Kang MK (2008) Capsaicin induces apoptosis and terminal differentiation in human glioma A172 cells. Life Sci 82:997–1003PubMedCrossRefGoogle Scholar
  24. Hidalgo M (2010) Pancreatic cancer. N Engl J Med 362:1605–1617PubMedCrossRefGoogle Scholar
  25. Holzer P (1991) Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 43:143–201PubMedGoogle Scholar
  26. Huang JK, Cheng HH, Huang CJ, Kuo CC, Chen WC, Liu SI, Hsu SS, Chang HT, Lu YC, Tseng LL, Chiang AJ, Chou CT, Jan CR (2006) Effect of capsazepine on cytosolic Ca(2+) levels and proliferation of human prostate cancer cells. Toxicol In Vitro Int J Publ Assoc BIBRA 20:567–574CrossRefGoogle Scholar
  27. Huang SP, Chen JC, Wu CC, Chen CT, Tang NY, Ho YT, Lo C, Lin JP, Chung JG, Lin JG (2009) Capsaicin-induced apoptosis in human hepatoma HepG2 cells. Anticancer Res 29:165–174PubMedGoogle Scholar
  28. Hwang JT, Lee YK, Shin JI, Park OJ (2009) Anti-inflammatory and anticarcinogenic effect of genistein alone or in combination with capsaicin in TPA-treated rat mammary glands or mammary cancer cell line. Ann N Y Acad Sci 1171:415–420PubMedCrossRefGoogle Scholar
  29. Jacobs BL, Lee CT, Montie JE (2010) Bladder cancer in 2010: how far have we come? CA Cancer J Clin 60:244–272PubMedCrossRefGoogle Scholar
  30. Jankovic B, Loblaw DA, Nam R (2010) Capsaicin may slow PSA doubling time: case report and literature review. Can Urol Assoc J 4:E9–E11PubMedGoogle Scholar
  31. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300PubMedCrossRefGoogle Scholar
  32. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRefGoogle Scholar
  33. Joung EJ, Li MH, Lee HG, Somparn N, Jung YS, Na HK, Kim SH, Cha YN, Surh YJ (2007) Capsaicin induces heme oxygenase-1 expression in HepG2 cells via activation of PI3K-Nrf2 signaling: NAD(P)H:quinone oxidoreductase as a potential target. Antioxid Redox Signal 9:2087–2098PubMedCrossRefGoogle Scholar
  34. Jun HS, Park T, Lee CK, Kang MK, Park MS, Kang HI, Surh YJ, Kim OH (2007) Capsaicin induced apoptosis of B16-F10 melanoma cells through down-regulation of Bcl-2. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc 45:708–715CrossRefGoogle Scholar
  35. Jung MY, Kang HJ, Moon A (2001) Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation. Cancer Lett 165:139–145PubMedCrossRefGoogle Scholar
  36. Kang HJ, Soh Y, Kim MS, Lee EJ, Surh YJ, Kim HR, Kim SH, Moon A (2003) Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras-transformed human breast epithelial cells. Int J Cancer 103:475–482PubMedCrossRefGoogle Scholar
  37. Keum YS, Jeong WS, Kong AN (2004) Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms. Mutat Res 555:191–202PubMedCrossRefGoogle Scholar
  38. Kim JD, Kim JM, Pyo JO, Kim SY, Kim BS, Yu R, Han IS (1997) Capsaicin can alter the expression of tumor forming-related genes which might be followed by induction of apoptosis of a Korean stomach cancer cell line, SNU-1. Cancer Lett 120:235–241PubMedCrossRefGoogle Scholar
  39. Kim CS, Park WH, Park JY, Kang JH, Kim MO, Kawada T, Yoo H, Han IS, Yu R (2004) Capsaicin, a spicy component of hot pepper, induces apoptosis by activation of the peroxisome proliferator-activated receptor gamma in HT-29 human colon cancer cells. J Med Food 7:267–273PubMedGoogle Scholar
  40. Kim YM, Hwang JT, Kwak DW, Lee YK, Park OJ (2007) Involvement of AMPK signaling cascade in capsaicin-induced apoptosis of HT-29 colon cancer cells. Ann N Y Acad Sci 1095:496–503PubMedCrossRefGoogle Scholar
  41. Kim MY, Trudel LJ, Wogan GN (2009) Apoptosis induced by capsaicin and resveratrol in colon carcinoma cells requires nitric oxide production and caspase activation. Anticancer Res 29:3733–3740PubMedGoogle Scholar
  42. Kim JY, Kim EH, Kim SU, Kwon TK, Choi KS (2010) Capsaicin sensitizes malignant glioma cells to TRAIL-mediated apoptosis via DR5 upregulation and survivin downregulation. Carcinogenesis 31:367–375PubMedCrossRefGoogle Scholar
  43. Lee YS, Nam DH, Kim JA (2000) Induction of apoptosis by capsaicin in A172 human glioblastoma cells. Cancer Lett 161:121–130PubMedCrossRefGoogle Scholar
  44. Lee JS, Chang JS, Lee JY, Kim JA (2004a) Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells. Arch Pharm Res 27:1147–1153PubMedCrossRefGoogle Scholar
  45. Lee YS, Kang YS, Lee JS, Nicolova S, Kim JA (2004b) Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the apoptotic cell death by capsaicin in HepG2 human hepatoma cells. Free Radic Res 38:405–412PubMedCrossRefGoogle Scholar
  46. Lee SH, Krisanapun C, Baek SJ (2010) NSAID-activated gene-1 as a molecular target for capsaicin-induced apoptosis through a novel molecular mechanism involving GSK3beta, C/EBPbeta and ATF3. Carcinogenesis 31:719–728PubMedCrossRefGoogle Scholar
  47. Li Q, Wang XH, Yang ZH, Wang HP, Yang ZW, Li SW, Zheng XM (2010) Induction of cell cycle arrest in bladder cancer RT4 cells by capsaicin. Zhonghua Yi Xue Za Zhi 90:1230–1233PubMedGoogle Scholar
  48. Lo YC, Yang YC, Wu IC, Kuo FC, Liu CM, Wang HW, Kuo CH, Wu JY, Wu DC (2005) Capsaicin-induced cell death in a human gastric adenocarcinoma cell line. World J Gastroenterol 11:6254–6257PubMedGoogle Scholar
  49. Lu HF, Chen YL, Yang JS, Yang YY, Liu JY, Hsu SC, Lai KC, Chung JG (2010) Antitumor activity of capsaicin on human colon cancer cells in vitro and colo 205 tumor xenografts in vivo. J Agric Food Chem 58:12999–13005PubMedCrossRefGoogle Scholar
  50. Malagarie-Cazenave S, Olea-Herrero N, Vara D, Diaz-Laviada I (2009) Capsaicin, a component of red peppers, induces expression of androgen receptor via PI3K and MAPK pathways in prostate LNCaP cells. FEBS Lett 583:141–147PubMedCrossRefGoogle Scholar
  51. Malagarie-Cazenave S, Olea-Herrero N, Vara D, Morell C, Diaz-Laviada I (2011) The vanilloid capsaicin induces IL-6 secretion in prostate PC-3 cancer cells. Cytokine 54:330–337PubMedCrossRefGoogle Scholar
  52. Matucci Cerinic M, McCarthy G, Lombardi A, Pignone A, Partsch G (1995) Neurogenic influences in arthritis: potential modification by capsaicin. J Rheumatol 22:1447–1449PubMedGoogle Scholar
  53. Modly CE, Das M, Don PS, Marcelo CL, Mukhtar H, Bickers DR (1986) Capsaicin as an in vitro inhibitor of benzo(a)pyrene metabolism and its DNA binding in human and murine keratinocytes. Drug Metab Dispos Biol Fate Chem 14:413–416PubMedGoogle Scholar
  54. Mori A, Lehmann S, O’Kelly J, Kumagai T, Desmond JC, Pervan M, McBride WH, Kizaki M, Koeffler HP (2006) Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res 66:3222–3229PubMedCrossRefGoogle Scholar
  55. Morre DJ, Chueh PJ, Morre DM (1995) Capsaicin inhibits preferentially the NADH oxidase and growth of transformed cells in culture. Proc Natl Acad Sci U S A 92:1831–1835PubMedCrossRefGoogle Scholar
  56. Patel PS, Varney ML, Dave BJ, Singh RK (2002a) Regulation of constitutive and induced NF-kappaB activation in malignant melanoma cells by capsaicin modulates interleukin-8 production and cell proliferation. J Interferon Cytokine Res 22:427–435PubMedCrossRefGoogle Scholar
  57. Patel PS, Yang S, Li A, Varney ML, Singh RK (2002b) Capsaicin regulates vascular endothelial cell growth factor expression by modulation of hypoxia inducing factor-1alpha in human malignant melanoma cells. J Cancer Res Clin Oncol 128:461–468PubMedCrossRefGoogle Scholar
  58. Pramanik KC, Boreddy SR, Srivastava SK (2011) Role of mitochondrial electron transport chain complexes in capsaicin mediated oxidative stress leading to apoptosis in pancreatic cancer cells. PLoS One 6:e20151PubMedCrossRefGoogle Scholar
  59. Sanchez AM, Sanchez MG, Malagarie-Cazenave S, Olea N, Diaz-Laviada I (2006) Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis 11:89–99PubMedCrossRefGoogle Scholar
  60. Sanchez AM, Malagarie-Cazenave S, Olea N, Vara D, Chiloeches A, Diaz-Laviada I (2007) Apoptosis induced by capsaicin in prostate PC-3 cells involves ceramide accumulation, neutral sphingomyelinase, and JNK activation. Apoptosis 12:2013–2024PubMedCrossRefGoogle Scholar
  61. Sanchez AM, Martinez-Botas J, Malagarie-Cazenave S, Olea N, Vara D, Lasuncion MA, Diaz-Laviada I (2008) Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: a microarray study. Biochem Biophys Res Commun 372:785–791PubMedCrossRefGoogle Scholar
  62. Satyanarayana MN (2006) Capsaicin and gastric ulcers. Crit Rev Food Sci Nutr 46:275–328PubMedCrossRefGoogle Scholar
  63. Shimazu T, Tsuji I, Inoue M, Wakai K, Nagata C, Mizoue T, Tanaka K, Tsugane S (2008) Alcohol drinking and gastric cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol 38:8–25PubMedCrossRefGoogle Scholar
  64. Shin DH, Kim OH, Jun HS, Kang MK (2008) Inhibitory effect of capsaicin on B16-F10 melanoma cell migration via the phosphatidylinositol 3-kinase/Akt/Rac1 signal pathway. Exp Mol Med 40:486–494PubMedCrossRefGoogle Scholar
  65. Sicuteri F, Fusco BM, Marabini S, Campagnolo V, Maggi CA, Geppetti P, Fanciullacci M (1989) Beneficial effect of capsaicin application to the nasal mucosa in cluster headache. Clin J Pain 5:49–53PubMedCrossRefGoogle Scholar
  66. Stavric B (1994) Role of chemopreventers in human diet. Clin Biochem 27:319–332PubMedCrossRefGoogle Scholar
  67. Stewart LA (2002) Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359:1011–1018PubMedCrossRefGoogle Scholar
  68. Sung NY, Choi KS, Park EC, Park K, Lee SY, Lee AK, Choi IJ, Jung KW, Won YJ, Shin HR (2007) Smoking, alcohol and gastric cancer risk in Korean men: the National Health Insurance Corporation Study. Br J Cancer 97:700–704PubMedCrossRefGoogle Scholar
  69. Surh YJ, Lee SS (1995) Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential. Life Sci 56:1845–1855PubMedCrossRefGoogle Scholar
  70. Talalay P, Fahey JW (2001) Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J Nutr 131:3027S–3033SPubMedGoogle Scholar
  71. Teel RW (1991) Effects of capsaicin on rat liver S9-mediated metabolism and DNA binding of aflatoxin. Nutr Cancer 15:27–32PubMedCrossRefGoogle Scholar
  72. Thoennissen NH, O’Kelly J, Lu D, Iwanski GB, La DT, Abbassi S, Leiter A, Karlan B, Mehta R, Koeffler HP (2010) Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway. Oncogene 29:285–296PubMedCrossRefGoogle Scholar
  73. Wang HM, Chueh PJ, Chang SP, Yang CL, Shao KN (2008) Effect of Ccapsaicin on tNOX (ENOX2) protein expression in stomach cancer cells. Biofactors 34:209–217PubMedCrossRefGoogle Scholar
  74. Watson CP, Evans RJ, Watt VR (1988) Post-herpetic neuralgia and topical capsaicin. Pain 33:333–340PubMedCrossRefGoogle Scholar
  75. Worrell RG, Moazami M, Worrell LA (1981) Hepatocellular carcinoma- etiologic considerations: a review of the literature. J National Med Assoc 73:601–607Google Scholar
  76. Yang KM, Pyo JO, Kim GY, Yu R, Han IS, Ju SA, Kim WH, Kim BS (2009) Capsaicin induces apoptosis by generating reactive oxygen species and disrupting mitochondrial transmembrane potential in human colon cancer cell lines. Cell Mol Biol Lett 14:497–510PubMedCrossRefGoogle Scholar
  77. Yang ZH, Wang XH, Wang HP, Hu LQ, Zheng XM, Li SW (2010) Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen species production and mitochondrial depolarization. Urology 75:735–741PubMedCrossRefGoogle Scholar
  78. Yoshitani SI, Tanaka T, Kohno H, Takashima S (2001) Chemoprevention of azoxymethane-induced rat colon carcinogenesis by dietary capsaicin and rotenone. Int J Oncol 19:929–939PubMedGoogle Scholar
  79. Zhang R, Humphreys I, Sahu RP, Shi Y, Srivastava SK (2008) In vitro and in vivo induction of apoptosis by capsaicin in pancreatic cancer cells is mediated through ROS generation and mitochondrial death pathway. Apoptosis 13:1465–1478PubMedCrossRefGoogle Scholar
  80. Ziglioli F, Frattini A, Maestroni U, Dinale F, Ciufifeda M, Cortellini P (2009) Vanilloid-mediated apoptosis in prostate cancer cells through a TRPV-1 dependent and a TRPV-1-independent mechanism. Acta Biomed Atenei Parmensis 80:13–20Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Biomedical Sciences and Cancer Biology Center, School of PharmacyTexas Tech University of Health Sciences CenterAmarilloUSA

Personalised recommendations