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Capsaicin and Its Potential Anticancer Mechanisms of Action

  • Ravindran Jaganathan
  • Boregowda Purushotham
  • Narayanaswamy Radhakrishnan
  • Mallappa Kumara Swamy
Chapter
  • 28 Downloads

Abstract

The human diet and its nutritional content may benefit in preventing several health issues. The enrichment of natural compounds in foodstuffs, having health supporting qualities is the present-day attention of by dieticians to explore a healthy food. Capsicum spp., are amongst the enormously consumed fruits worldwide, due to their bioactive compounds, capsaicinoids. They are used as nutrition additives and possess pharmacological properties. Hence, hot pepper fruits are widely screened for their pharmaceutical uses in human beings. Capsaicin is the major and commonly occurring capsaicinoids in chilli peppers, and it imparts hot pungent flavour to chillies. It possesses several important biological functions, especially analgesic properties. Capsaicin functions as a neuropeptide-releasing agent, and selective for sensory peripheral neurons. The compound is soluble in fats and readily engrossed through the skin. When used externally, capsaicin controls peripheral nerve ache. Numerous studies have focused on phytochemicals in human diet with anti-tumourigenic or anti-mutagenic phytochemical properties. Several studies performed in animals and cell lines showed the initiation of vigorous apoptosis by capsaicin. Also, it induces cell cycle arrest, reactive oxygen species production and disrupts the loss of mitochondrial membrane integrity, thereby activating caspases activities to promote apoptosis. Further, capsaicin can induce apoptosis in cancer cell lines through increasing the expression of p53 and c-myc genes. In this chapter, scientific evidences describing the potent anticancer efficacy and the mechanisms of action of capsaicin against various types of human cancers are discussed in detail.

Keywords

Cancer Cytotoxicity Inhibition Bioactive compound Therapeutics Medicines 

References

  1. Aa O, Ab S, Oi A, Oyagbemi AA, Azeez OI, Oyagbemi AA, Saba AB (2019) Capsaicin: a novel chemopreventive molecule and its underlying molecular mechanisms of action. Ind J Cancer 47(1):53–58.  https://doi.org/10.4103/0019-509X.58860CrossRefGoogle Scholar
  2. Aggarwal BB, Kunnumakkara AB, Harikumar KB, Tharakan ST, Sung B, Anand P, Words K (2008) Potential of spice-derived phytochemicals for cancer prevention. Planta Med 74(3):1560–1569.  https://doi.org/10.1055/s-2008-1074578CrossRefPubMedGoogle Scholar
  3. Aluru MR, Mazourek M, Landry LG, Curry J, Jahn M, Conell MA (2003) Differential expression of fatty acid synthase genes, Acl, Fat and Kas. Capsicum fruit. J Exp Bot 54:1655–1664Google Scholar
  4. Anand P, Bley K (2011) Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. Brit J Anaesth 107(4):490–502.  https://doi.org/10.1093/bja/aer260CrossRefPubMedGoogle Scholar
  5. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Devaki T (2009a) Lysosomal abnormalities during benzo(a)pyrene-induced experimental lung carcinogenesis--defensive role of capsaicin. Fund Clin Pharmacol 23(1):97–103.  https://doi.org/10.1111/j.1472-8206.2008.00637.xCrossRefGoogle Scholar
  6. Anandakumar P, Kamaraj S, Ramakrishnan G, Jagan S, Devaki T (2009b) Chemopreventive task of capsaicin against benzo(a)pyrene-induced lung cancer in Swiss albino mice. Basic Clin Pharmacol Toxicol 104(5):360–365.  https://doi.org/10.1111/j.1742-7843.2009.00387.xCrossRefPubMedGoogle Scholar
  7. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Asokkumar S, Naveenkumar C, Devaki T (2015) The anticancer role of capsaicin in experimentally induced lung carcinogenesis. J Pharmacopunct 18(2):19–25.  https://doi.org/10.3831/KPI.2015.18.011CrossRefGoogle Scholar
  8. Arora R, Gill NS, Chauhan G, Rana AC (2011) An overview about versatile molecule capsaicin. Int J Pharm Sci Drug Res 3:280–286Google Scholar
  9. Austin M, Elliott L, Nicolaou N, Grabowska A, Hulse RP (2017) Breast cancer induced nociceptor aberrant growth and collateral sensory axonal branching. Oncotarget 8(44):76606–76621CrossRefGoogle Scholar
  10. 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(11):1689–1696.  https://doi.org/10.1093/carcin/bgr191CrossRefPubMedPubMedCentralGoogle Scholar
  11. Basith S, Cui M, Hong S, Choi S (2016) Harnessing the therapeutic potential of capsaicin and its analogues in pain and other diseases. Molecules 21(8):966.  https://doi.org/10.3390/molecules21080966CrossRefPubMedCentralGoogle Scholar
  12. Bennett DJ, Kirby GW (1968) Constitution and biosynthesis of capsaicin. J Chem Soc C 2:442–446CrossRefGoogle Scholar
  13. Benzel J, Fendrich V (2018) Chemoprevention and treatment of pancreatic cancer : update and review of the literature. Digestion 97(4):275–287.  https://doi.org/10.1159/000485741CrossRefPubMedGoogle Scholar
  14. Bley K, Boorman G, Mohammad B, McKenzie D, Babbar S (2012) A comprehensive review of the carcinogenic and Anticarcinogenic potential of capsaicin. Toxicol Pathol 40(6):847–873.  https://doi.org/10.1177/0192623312444471CrossRefPubMedGoogle Scholar
  15. Bode AM, Dong Z (2011) The two faces of capsaicin. Cancer Res 71(8):2809–2814.  https://doi.org/10.1158/0008-5472.CAN-10-3756CrossRefPubMedGoogle Scholar
  16. Boreddy SR, Srivastava SK (2013) Pancreatic cancer chemoprevention by phytochemicals. Cancer Lett 334(1):86–94.  https://doi.org/10.1016/j.canlet.2012.10.020CrossRefPubMedGoogle Scholar
  17. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424.  https://doi.org/10.3322/caac.21492CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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(4):e10243–e10243.  https://doi.org/10.1371/journal.pone.0010243CrossRefPubMedPubMedCentralGoogle Scholar
  19. Cao S, Chen H, Xiang S, Hong J, Weng L, Zhu H, Liu Q (2015) Anti-Cancer effects and mechanisms of capsaicin in chili peppers. Am J Plant Sci 6(19):3075CrossRefGoogle Scholar
  20. Chakraborty S, Adhikary A, Mazumdar M, Mukherjee S, Bhattacharjee P, Guha D, Choudhuri T, Chattopadhyay S, Sa G, Sen A, Das T (2014a) Capsaicin-induced activation of p53-SMAR1 auto-regulatory loop down-regulates VEGF in non-small cell lung cancer to restrain angiogenesis. PLoS One 9(6):e99743–e99743.  https://doi.org/10.1371/journal.pone.0099743CrossRefPubMedPubMedCentralGoogle Scholar
  21. Chakraborty S, Mazumdar M, Mukherjee S, Bhattacharjee P (2014b) Restoration of p53/miR-34a regulatory axis decreases survival advantage and ensures Bax-dependent apoptosis of non-small cell lung carcinoma cells. FEBS Lett 588(4):549–559.  https://doi.org/10.1016/j.febslet.2013.11.040CrossRefPubMedGoogle Scholar
  22. 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. Human Exp Toxicol 30(10):1657–1665.  https://doi.org/10.1177/0960327110396530CrossRefGoogle Scholar
  23. Cho S, Lee H, Choi BY (2017) An updated review on molecular mechanisms underlying the anticancer effects of capsaicin. Food Sci Biotechnol 26(1):1–13.  https://doi.org/10.1007/s10068-017-0001-xCrossRefPubMedPubMedCentralGoogle Scholar
  24. Chou C, Wu Y, Wang Y, Chou M, Kuo S, Chen D (2009) Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway. Oncol Rep 21(3):665–671PubMedGoogle Scholar
  25. 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 1773:565–576.  https://doi.org/10.1016/j.bbamcr.2007.01.001CrossRefPubMedGoogle Scholar
  26. Clark R, Lee SH (2016) Anticancer properties of capsaicin against human cancer. Anticancer Res 36(3):837–843PubMedGoogle Scholar
  27. Cortright DN, Szallasi A (2004) Biochemical pharmacology of the vanilloid receptor TRPV1. An update. Eur J Biochem 271(10):1814–1819.  https://doi.org/10.1111/j.1432-1033.2004.04082.xCrossRefGoogle Scholar
  28. Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O’Connell MA (1999) Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent Capsicum spp. Plant Sci 148:47–57CrossRefGoogle Scholar
  29. Derry S, Rice AS, Cole P, Tan T, Moore RA (2017) Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database Syst Rev 1:CD007393.  https://doi.org/10.1002/14651858.CD007393.pub4CrossRefPubMedGoogle Scholar
  30. Díaz-Laviada I, Rodríguez-Henche N (2014) The potential antitumor effects of capsaicin. In: Abdel-Salam O (ed) capsaicin as a therapeutic molecule. Progress in drug research, vol vol 68. Springer, BaselGoogle Scholar
  31. Estrada B, Pomar F, Díaz J, Merino F, Bernal MA (1999) Pungency levels in fruits of the pardon pepper with different water supply. Hort Sci 81:385–396CrossRefGoogle Scholar
  32. Ferreira AK, Tavares MT, Pasqualoto KF, de Azevedo RA, Teixeira SF, Ferreira-Junior WA, Bertin AM, de-Sá-Junior PL, Barbuto JA, Figueiredo CR, Cury Y (2015) RPF151, a novel capsaicin-like analogue: in vitro studies and in vivo preclinical antitumor evaluation in a breast cancer model. Tumour Biol 36(9):7251–7267.  https://doi.org/10.1007/s13277-015-3441-zCrossRefPubMedGoogle Scholar
  33. Friedman JR, Nolan NA, Brown KC, Miles SL, Akers AT, Colclough KW, Seidler JM, Rimoldi JM, Valentovic MA, Dasgupta P (2018) Minireviews anticancer activity of natural and synthetic capsaicin analogs. J Pharmacol Exp Ther 364(3):462–473.  https://doi.org/10.1124/jpet.117.243691CrossRefPubMedPubMedCentralGoogle Scholar
  34. Gonzalez-Reyes LE, Ladas TP, Chiang CC, Durand DM (2013) TRPV1 antagonist capsazepine suppresses 4-AP-induced epileptiform activity in vitro and electrographic seizures in vivo. Exp Neurol 250:321–332.  https://doi.org/10.1016/j.expneurol.2013.10.010CrossRefPubMedPubMedCentralGoogle Scholar
  35. González-Zamora A, Sierra-Campos E, Pérez-Morales R, Vázquez-Vázquez C, Gallegos-Robles MA, López-Martínez JD, García-Hernández JL (2015) Measurement of capsaicinoids in chiltepin hot pepper: a comparison study between spectrophotometric method and high performance liquid chromatography analysis. J Chem 2015:1–10.  https://doi.org/10.1155/2015/709150CrossRefGoogle Scholar
  36. Grothey A, Adjei AA, Alberts SR, Perez EA, Jaeckle KA, Loprinzi CL, Sargent DJ, Sloan JA, Buckner JC (2008) North central Cancer treatment group--achievements and perspectives. Sem Oncol 35(5):530–544.  https://doi.org/10.1053/j.seminoncol.2008.07.006CrossRefGoogle Scholar
  37. Hecht SS (1999) Tobacco smoke carcinogens and lung Cancer. J Nat Cancer Inst 91(14):1194–1210.  https://doi.org/10.1093/jnci/91.14.1194CrossRefPubMedGoogle Scholar
  38. Ho JSL, Ma W, Mao DYL, Benchimol S (2005) p53-dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol Cell Biol 25(17):7423–7431.  https://doi.org/10.1128/MCB.25.17.7423-7431.2005CrossRefPubMedPubMedCentralGoogle Scholar
  39. Huang JK, Cheng HH, Huang CJ, Kuo CC, Chen WC, Liu SI, Jan CR (2006) Effect of capsazepine on cytosolic Ca(2+) levels and proliferation of human prostate cancer cells. Toxicol In Vitro 20(5):567–574.  https://doi.org/10.1016/j.tiv.2005.09.014CrossRefPubMedGoogle Scholar
  40. Huh HC, Lee SY, Lee SK, Park NH, Han IS (2011) Capsaicin induces apoptosis of cisplatin-resistant stomach cancer cells by causing degradation of cisplatin-inducible Aurora-a protein. Nutr Cancer 63(7):1095–1103.  https://doi.org/10.1080/01635581.2011.607548CrossRefPubMedGoogle Scholar
  41. Hwang J-T, Kwak DW, Lin SK, Kim HM, Kim YM, Park OJ (2007) Resveratrol induces apoptosis in chemoresistant cancer cells via modulation of AMPK signaling pathway. Ann N Y Acad Sci 1095:441–448.  https://doi.org/10.1196/annals.1397.047CrossRefPubMedGoogle Scholar
  42. Hwang J-T, 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 1171:415–420.  https://doi.org/10.1111/j.1749-6632.2009.04696.xCrossRefPubMedGoogle Scholar
  43. Hyoung KL, Kim TI, Noh SH, Kim JY, Paik HD, Kim CH (2006) Pylori Helicobacter. J Microbiol Biotechnol 16(7):1078–1083Google Scholar
  44. Jankovic B, Loblaw DA, Nam R (2010) Capsaicin may slow PSA doubling time: case report and literature review. Can Urol Assoc J 4(1):E9–E11.  https://doi.org/10.5489/cuaj.784CrossRefPubMedPubMedCentralGoogle Scholar
  45. Jara-Oseguera A, Simon SA, Rosenbaum T (2008) TRPV1: on the road to pain relief. Curr Mol Pharmacol 1(3):255–269. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20021438CrossRefGoogle Scholar
  46. Jung SH, Kim HJ, Oh GS, Shen A, Lee S, Choe SK, Park R, So HS (2014) Capsaicin ameliorates cisplatin-induced renal injury through induction of heme oxygenase-1. Mol Cells 37(3):234–240.  https://doi.org/10.14348/molcells.2014.2322CrossRefPubMedPubMedCentralGoogle Scholar
  47. Katritzky AR, Xu YJ, Vakulenko AV, Wilcox AL, Bley KR (2003) Model compounds of caged capsaicin: design, synthesis, and photoreactivity. J Org Chem 68:9100–9104CrossRefGoogle Scholar
  48. Kedei N, Szabo T, Lile JD, Treanor JJ, Olah Z, Iadarola MJ, Blumberg PM (2001) Analysis of the native quaternary structure of vanilloid receptor 1. J Biol Chem 276(30):28613–28619CrossRefGoogle Scholar
  49. Kehie M, Kumaria S, Tandon P (2014) Manipulation of culture strategies to enhance capsaicin biosynthesis in suspension and immobilized cell cultures of Capsicum chinense Jacq. cv. Naga King Chili. Bioprocess Biosyst Eng 37:1055–1063CrossRefGoogle Scholar
  50. Kehie M, Kumaria S, Tandon P, Ramchiary N (2015) Biotechnological advances on in vitro capsaicinoids biosynthesis in capsicum: a review. Phytochem Rev 14:189–201CrossRefGoogle Scholar
  51. Kim S, Moon A (2004) Capsaicin-induced apoptosis of H-ras-transformed human breast epithelial cells is Rac-dependent via ROS generation. Arch Pharm Res 27(8):845–849CrossRefGoogle Scholar
  52. 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(2):235–241CrossRefGoogle Scholar
  53. 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 1095:496–503.  https://doi.org/10.1196/annals.1397.053CrossRefPubMedGoogle Scholar
  54. 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(10):3733–3740PubMedGoogle Scholar
  55. Kodydkova J, Vavrova L, Stankova B, Macasek J, Krechler T, Zak A (2013) Antioxidant status and oxidative stress markers in pancreatic cancer and chronic pancreatitis. Pancreas 42(4):614–621.  https://doi.org/10.1097/MPA.0b013e318288360aCrossRefPubMedGoogle Scholar
  56. Kumar S, Singh A, Sharma M (2013) Mechanisms and clinical uses of capsaicin. Eur J Pharmacol 720(1–3):55–62.  https://doi.org/10.1016/j.ejphar.2013.10.053CrossRefGoogle Scholar
  57. Lau JK, Brown KC, Dom AM, Witte TR, Thornhill BA, Crabtree CM, Perry HE, Brown JM, Ball JG, Creel RG, Damron CL (2014) Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway. Apoptosis 19(8):1190–1201.  https://doi.org/10.1007/s10495-014-1007-yCrossRefPubMedPubMedCentralGoogle Scholar
  58. Lee MJ, Kee KH, Suh CH, Lim SC, Oh SH (2009) Capsaicin-induced apoptosis is regulated by endoplasmic reticulum stress- and calpain-mediated mitochondrial cell death pathways. Toxicology 264(3):205–214.  https://doi.org/10.1016/j.tox.2009.08.012CrossRefPubMedGoogle Scholar
  59. 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(4):719–728.  https://doi.org/10.1093/carcin/bgq016CrossRefPubMedPubMedCentralGoogle Scholar
  60. Lee YH, Chen HY, Su LJ, Chueh PJ (2015) Sirtuin 1 (SIRT1) Deacetylase activity and NAD(+)/NADH ratio are imperative for capsaicin-mediated programmed cell death. J Agric Food Chem 63(33):7361–7370.  https://doi.org/10.1021/acs.jafc.5b02876CrossRefPubMedGoogle Scholar
  61. Leete E, Louden MCL (1968) Biosynthesis of capsaicin and dihydrocapsaicin in Capsicum frutescens. J Am Chem Soc 90:6837–6841CrossRefGoogle Scholar
  62. Lin C, Lu W, Wang C, Chan Y, Chen M (2013a) Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells. BMC Compl Alt Med 13(1):1.  https://doi.org/10.1186/1472-6882-13-46CrossRefGoogle Scholar
  63. Lin S, Zhang J, Chen H, Chen K, Lai F, Luo J, Wang Z, Bu H, Zhang R, Li H, Tong H (2013b) Involvement of endoplasmic reticulum stress in capsaicin-induced apoptosis of human pancreatic Cancer cells. Evid Based Compl Alt Med 2013:1–12Google Scholar
  64. 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(40):6254–6257.  https://doi.org/10.3748/wjg.v11.i40.6254CrossRefPubMedPubMedCentralGoogle Scholar
  65. 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(24):12999–13005.  https://doi.org/10.1021/jf103335wCrossRefPubMedGoogle Scholar
  66. Malagarie-Cazenave S, Olea-Herrero N, Vara D, Morell C, Díaz-Laviada I (2011) The vanilloid capsaicin induces IL-6 secretion in prostate PC-3 cancer cells. Cytokine 54(3):330–337.  https://doi.org/10.1016/j.cyto.2011.03.010CrossRefPubMedGoogle Scholar
  67. Moghadaszadeh-ardebili S (2016) The anticancer mechanism of capsaicin on various cancer cell lines. Ann Res Antioxiox 1(1):1–5Google Scholar
  68. 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(6):3222–3229.  https://doi.org/10.1158/0008-5472.CAN-05-0087CrossRefPubMedGoogle Scholar
  69. Morita A, Iwasaki Y, Kobata K, Iida T, Higashi T, Oda K, Suzuki A, Narukawa M, Sasakuma S, Yokogoshi H, Yazawa S (2006) Lipophilicity of capsaicinoids and capsinoids influences the multiple activation process of rat TRPV1. Life Sci 79(24):2303–2310.  https://doi.org/10.1016/j.lfs.2006.07.024CrossRefPubMedGoogle Scholar
  70. 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(6):1831–1835.  https://doi.org/10.1073/pnas.92.6.1831CrossRefPubMedPubMedCentralGoogle Scholar
  71. Park SY, Kim JY, Lee SM, Jun CH, Cho SB, Park CH, Joo YE, Kim HS, Choi SK, Rew JS (2014) Capsaicin induces apoptosis and modulates MAPK signaling in human gastric cancer cells. Mol Med Rep 9(2):499–502.  https://doi.org/10.3892/mmr.2013.1849CrossRefPubMedGoogle Scholar
  72. Patowary P, Pratim M, Zaman K, Raju PS (2017) Biomedicine & Pharmacotherapy Research progress of capsaicin responses to various pharmacological challenges. Biomed Pharmacother 96:1501–1512.  https://doi.org/10.1016/j.biopha.2017.11.124CrossRefGoogle Scholar
  73. Pinchot SN, Holen K, Sippel RS, Chen H (2008) Carcinoid tumors. Oncologist 13(12):1255–1269.  https://doi.org/10.1634/theoncologist.2008-0207CrossRefPubMedPubMedCentralGoogle Scholar
  74. Pramanik KC, Srivastava SK (2012) Complex dissociation by capsaicin causes pancreatic tumor growth suppression by inducing apoptosis. Antioxid Redox Signal 17(10):1417–1432.  https://doi.org/10.1089/ars.2011.4369CrossRefPubMedPubMedCentralGoogle Scholar
  75. Pramanik KC, Srivastava SK (2013) In: Srivastava SK (ed) Role of capsaicin in cancer prevention role of capsaicin in Cancer prevention. Springer, Dordrecht, pp 1–18.  https://doi.org/10.1007/978-94-007-6317-3CrossRefGoogle Scholar
  76. 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(5):e20151.  https://doi.org/10.1371/journal.pone.0020151CrossRefPubMedPubMedCentralGoogle Scholar
  77. Pramanik KC, Fofaria NM, Gupta P, Ranjan A, Kim SH, Srivastava SK (2015) Inhibition of beta-catenin signaling suppresses pancreatic tumor growth by disrupting nuclear beta-catenin/TCF-1 complex: critical role of STAT-3. Oncotarget 6(13):11561–11574.  https://doi.org/10.18632/oncotarget.3427CrossRefPubMedPubMedCentralGoogle Scholar
  78. Prasad BN, Kumar V, Gururaj HB, Parimalan R, Giridhar P, Ravishankar GA (2006) Characterization of capsaicin synthase and identification of its gene (csy1) for pungency factor capsaicin in pepper (Capsicum sp.). Proc Natl Acad Sci 103(36):13315–13320CrossRefGoogle Scholar
  79. Rahman MJ, Inden H, Hossain MM (2012) Capsaicin content in sweet pepper (Capsicum annuum L.) under temperature stress. Acta Hort 936:195–201CrossRefGoogle Scholar
  80. Ramos-torres Á, Bort A, Morell C, Rodríguez-henche N (2015) The pepper’s natural ingredient capsaicin induces autophagy blockage in prostate cancer cells. Oncotarget 7(2):1569CrossRefGoogle Scholar
  81. Reyes-escogido MDL, Gonzalez-mondragon EG, Vazquez-tzompantzi E (2011) Chemical and pharmacological aspects of capsaicin. Molecules 16(2):1253–1270.  https://doi.org/10.3390/molecules16021253CrossRefPubMedCentralGoogle Scholar
  82. Rollyson WD, Stover CA, Brown KC, Perry HE, Stevenson CD, McNees CA, Ball JG, Valentovic MA, Dasgupta P (2014) Bioavailability of capsaicin and its implications for drug delivery. J Control Rel 196:96–105.  https://doi.org/10.1016/j.jconrel.2014.09.027CrossRefGoogle Scholar
  83. Satyanarayana MN (2006) Capsaicin and gastric ulcers. Crit Rev Food Sci Nutr 46(4):275–328.  https://doi.org/10.1080/1040-830491379236CrossRefPubMedGoogle Scholar
  84. Shim Y, Song JM (2015) Quantum dot nanoprobe-based high-content monitoring of notch pathway inhibition of breast cancer stem cell by capsaicin. Mol Cell Probes 29(6):376–381.  https://doi.org/10.1016/j.mcp.2015.09.004CrossRefPubMedGoogle Scholar
  85. Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP (2018) Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res 10:239–248.  https://doi.org/10.2147/CMAR.S149619CrossRefPubMedPubMedCentralGoogle Scholar
  86. Skrzypski M, Sassek M, Abdelmessih S, Mergler S, Grötzinger C, Metzke D, Wojciechowicz T (2014) Capsaicin induces cytotoxicity in pancreatic neuroendocrine tumor cells via mitochondrial action. Cell Signal 26(1):41–48.  https://doi.org/10.1016/j.cellsig.2013.09.014CrossRefPubMedGoogle Scholar
  87. Sokolova O, Naumann M (2017) NF-κ B signaling in gastric cancer. Toxins 9(4).  https://doi.org/10.3390/toxins9040119
  88. Surh Y (2002) More than spice : capsaicin in hot chili peppers makes tumor cells commit suicide. J Natl Cancer Inst 94(17):1263–1265CrossRefGoogle Scholar
  89. Surh YJ, Lee SS (1996) Capsaicin, a spicy component of hot pepper, induces apoptosis by activation of the peroxisome proliferator-activated receptor in HT-29 human Colon Cancer cells. Food Chem Toxicol 34(3):313–316.  https://doi.org/10.1016/j.ejphar.2013.10.053CrossRefPubMedGoogle Scholar
  90. 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(2):285–296.  https://doi.org/10.1038/onc.2009.335CrossRefPubMedGoogle Scholar
  91. Thomas KC, Ethirajan M, Shahrokh K, Sun H, Lee J, Cheatham TE, Yost GS, Reilly CA (2011) Structure-activity relationship of capsaicin analogs and transient receptor potential Vanilloid 1-mediated human lung epithelial cell toxicity. J Pharmacol Exp Ther 337(2):400–410.  https://doi.org/10.1124/jpet.110.178491CrossRefPubMedPubMedCentralGoogle Scholar
  92. Thomas KC, Roberts JK, Deering-Rice CE, Romero EG, Dull RO, Lee J, Yost GS, Reilly CA (2012) Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung cell death in vitro and lung injury. Am J Phys Lung Cell Mol Phys 302(1):L111–L119.  https://doi.org/10.1152/ajplung.00231.2011CrossRefGoogle Scholar
  93. Tominaga M, Tominaga T (2005) Structure and function of TRPV1. Eur J Phys 451(1):143–150.  https://doi.org/10.1007/s00424-005-1457-8CrossRefGoogle Scholar
  94. Van Haute C, De Ridder D, Nilius B (2010) TRP channels in human prostate. Sci World J 10:1597–1611CrossRefGoogle Scholar
  95. Venier NA, Colquhoun AJ, Sasaki H, Kiss A, Sugar L, Adomat H, Fleshner NE, Klotz LH, Venkateswaran V (2015) Capsaicin: a novel radio-sensitizing agent for prostate cancer. Prostate 75(2):113–125.  https://doi.org/10.1002/pros.22896CrossRefPubMedGoogle Scholar
  96. Wang HM, Chuang SM, Su YC, Li YH, Chueh PJ (2011) Down-regulation of tumor-associated NADH oxidase, tNOX (ENOX2): enhances capsaicin-induced inhibition of gastric cancer cell growth. Cell Biochem Biophys 61(2):355–366.  https://doi.org/10.1007/s12013-011-9218-0CrossRefPubMedGoogle Scholar
  97. Wang P, Sun YC, Lu WH, Huang P, Hu Y (2015) Selective killing of K-ras-transformed pancreatic cancer cells by targeting NAD(P)H oxidase. Chin J Cancer 34(4):166–176.  https://doi.org/10.1186/s40880-015-0012-zCrossRefPubMedGoogle Scholar
  98. Xie L, Xiang GH, Tang T, Tang Y, Zhao LY, Liu D, Zhang YR, Tang JT, Zhou S, Wu DH (2016) Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+mediated mitochondrial pathway. Mol Med Rep 14(5):4198–4208.  https://doi.org/10.3892/mmr.2016.5784CrossRefPubMedPubMedCentralGoogle Scholar
  99. 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(3):497–510.  https://doi.org/10.2478/s11658-009-0016-2CrossRefPubMedPubMedCentralGoogle Scholar
  100. Yang J, Li TZ, Xu GH, Luo BB, Chen YX, Zhang T (2013) Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways. Neoplasma 60(4):364–372.  https://doi.org/10.4149/neoCrossRefPubMedGoogle Scholar
  101. 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(12):1465–1478.  https://doi.org/10.1007/s10495-008-0278-6CrossRefPubMedGoogle Scholar
  102. Zhang R, Humphreys I, Sahu RP, Shi Y, Srivastava SK (2009) 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(12):1465–1478.  https://doi.org/10.1007/s10495-008-0278-6CrossRefGoogle Scholar
  103. Zheng J (2013) Molecular mechanism of TRP channels. Compr Physiol 3(1):221–242PubMedPubMedCentralGoogle Scholar
  104. Zheng L, Chen J, Ma Z, Liu W, Yang F, Yang Z, Li L (2015) Capsaicin causes inactivation and degradation of the androgen receptor by inducing the restoration of miR-449a in prostate cancer. Oncol Rep 34(2):1027–1034.  https://doi.org/10.3892/or.2015.4055CrossRefPubMedGoogle Scholar
  105. Ziglioli F, Frattini A, Maestroni U, Dinale F (2009) Vanilloid-mediated apoptosis in prostate cancer cells through aTRPV-1 dependent and a TRPV-1-independent mechanism. Acta Bio Medica Atenei Parmensis 80(1):13–20PubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Ravindran Jaganathan
    • 1
  • Boregowda Purushotham
    • 2
  • Narayanaswamy Radhakrishnan
    • 3
  • Mallappa Kumara Swamy
    • 2
  1. 1.Pathology Unit, Faculty of Medicine, Royal College of Medicine PerakUniversiti Kuala LumpurIpohMalaysia
  2. 2.Department of BiotechnologyEast West First Grade CollegeBengaluruIndia
  3. 3.Department of BiochemistrySt. Peter’s Institute of Higher Education and Research (SPIHER)ChennaiIndia

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