Skip to main content
SpringerLink
Log in

The Potential Antitumor Effects of Capsaicin

  • Chapter
  • First Online:
Capsaicin as a Therapeutic Molecule

Part of the book series: Progress in Drug Research ((PDR,volume 68))

Abstract

Capsaicin, one of the major pungent ingredients found in red peppers, has been recently demonstrated to induce apoptosis in many types of malignant cell lines including colon adenocarcinoma, pancreatic cancer, hepatocellular carcinoma, prostate cancer, breast cancer, and many others. The mechanism whereby capsaicin induces apoptosis in cancer cells is not completely elucidated but involves intracellular calcium increase, reactive oxygen species generation, disruption of mitochondrial membrane transition potential, and activation of transcription factors such as NFκB and STATS. Recently, a role for the AMP-dependent kinase (AMPK) and autophagy pathways in capsaicin-triggered cell death has been proposed. In addition, capsaicin shows antitumor activity in vivo by reducing the growth of many tumors induced in mice. In this chapter, we report the last advances performed in the antitumor activity of capsaicin and review the main signaling pathways involved.

Conflict of Interest. Authors declare that there is no conflict of interest.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alers S, Loffler AS, Wesselborg S, Stork B (2012) Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 32:2–11

    CAS  PubMed Central  PubMed  Google Scholar 

  • Alothman ZA, Wabaidur SM, Khan MR, Abdel Ghafar A, Habila MA, Ahmed YB (2012) Determination of capsaicinoids in Capsicum species using ultra performance liquid chromatography-mass spectrometry. J Sep Sci 35:2892–2896

    CAS  PubMed  Google Scholar 

  • Athanasiou A, Smith PA, Vakilpour S, Kumaran NM, Turner AE, Bagiokou D et al (2007) Vanilloid receptor agonists and antagonists are mitochondrial inhibitors: how vanilloids cause non-vanilloid receptor mediated cell death. Biochem Biophys Res Commun 354:50–55

    CAS  PubMed  Google Scholar 

  • Babbar S, Chanda S, Bley K (2010) Inhibition and induction of human cytochrome P450 enzymes in vitro by capsaicin. Xenobiotica 40:807–816

    CAS  PubMed  Google Scholar 

  • Becatti M, Prignano F, Fiorillo C, Pescitelli L, Nassi P, Lotti T et al (2010) The involvement of Smac/DIABLO, p53, NF-kB, and MAPK pathways in apoptosis of keratinocytes from perilesional vitiligo skin: protective effects of curcumin and capsaicin. Antioxid Redox Signal 13:1309–1321

    CAS  PubMed  Google Scholar 

  • Biggs JE, Yates JM, Loescher AR, Clayton NM, Boissonade FM, Robinson PP (2007) Vanilloid receptor 1 (TRPV1) expression in lingual nerve neuromas from patients with or without symptoms of burning pain. Brain Res 1127:59–65

    CAS  PubMed  Google Scholar 

  • Bochalli R (1952) To the 50th anniversary of death of Rudolf Wirchow. Hippokrates 23:647–649

    CAS  PubMed  Google Scholar 

  • Bosneaga E, Kim C, Shen B, Watanabe T, Morre DM, Morre DJ (2008) ECTO-NOX (ENOX) proteins of the cell surface lack thioredoxin reductase activity. BioFactors 34:245–251

    PubMed  Google Scholar 

  • Brown KC, Witte TR, Hardman WE, Luo H, Chen YC, Carpenter AB et al (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:e10243

    PubMed Central  PubMed  Google Scholar 

  • Caffarel MM, Sarrio D, Palacios J, Guzman M, Sanchez C (2006) Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res 66:6615–6621

    CAS  PubMed  Google Scholar 

  • Caprodossi S, Amantini C, Nabissi M, Morelli MB, Farfariello V, Santoni M et al (2011) Capsaicin promotes a more aggressive gene expression phenotype and invasiveness in null-TRPV1 urothelial cancer cells. Carcinogenesis 32:686–694

    CAS  PubMed  Google Scholar 

  • Cardaci S, Filomeni G, Ciriolo MR (2012) Redox implications of AMPK-mediated signal transduction beyond energetic clues. J Cell Sci 125:2115–2125

    CAS  PubMed  Google Scholar 

  • Carter HB, Albertsen PC, Barry MJ, Etzioni R, Freedland SJ, Greene KL et al (2013) Early detection of prostate cancer: AUA guideline. J Urol 190:419–426

    Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    CAS  PubMed  Google Scholar 

  • Crane FL, Low H (2008) Reactive oxygen species generation at the plasma membrane for antibody control. Autoimmun Rev 7:518–522

    CAS  PubMed  Google Scholar 

  • Cui Y, Yang F, Cao X, Yarov-Yarovoy V, Wang K, Zheng J (2012) Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations. J Gen Physiol 139:273–283

    CAS  PubMed Central  PubMed  Google Scholar 

  • Czifra G, Varga A, Nyeste K, Marincsak R, Toth BI, Kovacs I et al (2009) Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma. J Cancer Res Clin Oncol 135:507–514

    CAS  PubMed  Google Scholar 

  • 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 30:1657–1665

    CAS  PubMed  Google Scholar 

  • Choi CH, Jung YK, Oh SH (2010a) 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 78:114–125

    CAS  PubMed  Google Scholar 

  • Choi CH, Jung YK, Oh SH (2010b) Selective induction of catalase-mediated autophagy by dihydrocapsaicin in lung cell lines. Free Radic Biol Med 49:245–257

    CAS  PubMed  Google Scholar 

  • Choi SE, Kim TH, Yi SA, Hwang YC, Hwang WS, Choe SJ et al (2011) Capsaicin attenuates palmitate-induced expression of macrophage inflammatory protein 1 and interleukin 8 by increasing palmitate oxidation and reducing c-Jun activation in THP-1 (human acute monocytic leukemia cell) cells. Nutr Res 31:468–478

    CAS  PubMed  Google Scholar 

  • 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 21:665–671

    CAS  PubMed  Google Scholar 

  • Chueh PJ, Wu LY, Morre DM, Morre DJ (2004) tNOX is both necessary and sufficient as a cellular target for the anticancer actions of capsaicin and the green tea catechin (-)-epigallocatechin-3-gallate. BioFactors 20:235–249

    PubMed  Google Scholar 

  • de Sa Junior PL, Pasqualoto KF, Ferreira AK, Tavares MT, Damiao MC, de Azevedo RA et al (2013) RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells. Toxicol Appl Pharmacol 266:385–398

    Google Scholar 

  • Dikic I, Johansen T, Kirkin V (2010) Selective autophagy in cancer development and therapy. Cancer Res 70:3431–3434

    CAS  PubMed  Google Scholar 

  • Dou D, Ahmad A, Yang H, Sarkar FH (2011) Tumor cell growth inhibition is correlated with levels of capsaicin present in hot peppers. Nutr Cancer 63:272–281

    CAS  PubMed  Google Scholar 

  • Eisenberg-Lerner A, Kimchi A (2009) The paradox of autophagy and its implication in cancer etiology and therapy. Apoptosis 14:376–391

    Google Scholar 

  • Glick D, Barth S, Macleod KF (2010) Autophagy: cellular and molecular mechanisms. J Pathol 221:3–12

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hage-Sleiman R, Esmerian MO, Kobeissy H, Dbaibo G (2013) p53 and ceramide as collaborators in the stress response. Int J Mol Sci 14:4982–5012

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hail N Jr (2003) Mechanisms of vanilloid-induced apoptosis. Apoptosis 8:251–262

    CAS  PubMed  Google Scholar 

  • Hail N Jr, Lotan R (2002) Examining the role of mitochondrial respiration in vanilloid-induced apoptosis. J Natl Cancer Inst 94:1281–1292

    CAS  PubMed  Google Scholar 

  • Hardie DG, Alessi DR (2013) LKB1 and AMPK and the cancer-metabolism link-ten years after. BMC Biol 11:36

    PubMed Central  PubMed  Google Scholar 

  • Hardie DG, Ross FA, Hawley SA (2012) AMP-activated protein kinase: a target for drugs both ancient and modern. Chem Biol 19:1222–1236

    CAS  PubMed  Google Scholar 

  • Horoszewicz JS, Leong SS, Kawinski E, Karr JP, Rosenthal H, Chu TM et al (1983) LNCaP model of human prostatic carcinoma. Cancer Res 43:1809–1818

    CAS  PubMed  Google Scholar 

  • Hsu CL, Yen GC (2007) Effects of capsaicin on induction of apoptosis and inhibition of adipogenesis in 3T3-L1 cells. J Agric Food Chem 55:1730–1736

    CAS  PubMed  Google Scholar 

  • Huang SP, Chen JC, Wu CC, Chen CT, Tang NY, Ho YT et al (2009) Capsaicin-induced apoptosis in human hepatoma HepG2 cells. Anticancer Res 29:165–174

    CAS  PubMed  Google Scholar 

  • Ip SW, Lan SH, Lu HF, Huang AC, Yang JS, Lin JP et al (2012) Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress. Hum Exp Toxicol 31:539–549

    CAS  PubMed  Google Scholar 

  • Ito K, Nakazato T, Yamato K, Miyakawa Y, Yamada T, Hozumi N et al (2004) 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 64:1071–1078

    CAS  PubMed  Google Scholar 

  • Iype PT, Iype LE, Verma M, Kaighn ME (1998) Establishment and characterization of immortalized human cell lines from prostatic carcinoma and benign prostatic hyperplasia. Int J Oncol 12:257–263

    CAS  PubMed  Google Scholar 

  • Jankovic B, Loblaw DA, Nam R (2010) Capsaicin may slow PSA doubling time: case report and literature review. Can Urol Assoc J 4:E9–E11

    PubMed Central  PubMed  Google Scholar 

  • Jiang Z, Gorenstein NM, Morre DM, Morre DJ (2008) Molecular cloning and characterization of a candidate human growth-related and time-keeping constitutive cell surface hydroquinone (NADH) oxidase. Biochemistry 47:14028–14038

    CAS  PubMed  Google Scholar 

  • Jordt SE, Julius D (2002) Molecular basis for species-specific sensitivity to “hot” chili peppers. Cell 108:421–430

    CAS  PubMed  Google Scholar 

  • Joung EJ, Li MH, Lee HG, Somparn N, Jung YS, Na HK et al (2007) Capsaicin induces heme oxygenase-1 expression in HepG2 cells via activation of PI3 K-Nrf2 signaling: NAD(P)H:quinone oxidoreductase as a potential target. Antioxid Redox Signal 9:2087–2098

    CAS  PubMed  Google Scholar 

  • Kang JH, Goto T, Han IS, Kawada T, Kim YM, Yu R (2010) Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesity (Silver Spring) 18:780–787

    CAS  Google Scholar 

  • Kim CS, Park WH, Park JY, Kang JH, Kim MO, Kawada T et al (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 7:267–273

    CAS  PubMed  Google Scholar 

  • Kim MY (2012) Nitric oxide triggers apoptosis in A375 human melanoma cells treated with capsaicin and resveratrol. Mol Med Rep 5:585–591

    CAS  PubMed  Google Scholar 

  • 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 29:3733–3740

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Lee GR, Shin MK, Yoon DJ, Kim AR, Yu R, Park NH et al (2013) Topical application of capsaicin reduces visceral adipose fat by affecting adipokine levels in high-fat diet-induced obese mice. Obesity (Silver Spring) 21:115–122

    Google Scholar 

  • 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 264:205–214

    CAS  PubMed  Google Scholar 

  • Lee SH, Richardson RL, Dashwood RH, Baek SJ (2012) Capsaicin represses transcriptional activity of beta-catenin in human colorectal cancer cells. J Nutr Biochem 23:646–655

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee YS, Kang YS, Lee JS, Nicolova S, Kim JA (2004) Involvement of NADPH oxidase-mediated generation of reactive oxygen species in the apototic cell death by capsaicin in HepG2 human hepatoma cells. Free Radic Res 38:405–412

    CAS  PubMed  Google Scholar 

  • Li S, Bode AM, Zhu F, Liu K, Zhang J, Kim MO et al (2011) TRPV1-antagonist AMG9810 promotes mouse skin tumorigenesis through EGFR/Akt signaling. Carcinogenesis 32:779–785

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lin CH, Lu WC, Wang CW, Chan YC, Chen MK (2013) Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells. BMC Complement Altern Med 13:46

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lishko PV, Procko E, Jin X, Phelps CB, Gaudet R (2007) The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron 54:905–918

    CAS  PubMed  Google Scholar 

  • Liu NC, Hsieh PF, Hsieh MK, Zeng ZM, Cheng HL, Liao JW et al (2012) Capsaicin-mediated tNOX (ENOX2) up-regulation enhances cell proliferation and migration in vitro and in vivo. J Agric Food Chem 60:2758–2765

    CAS  PubMed  Google Scholar 

  • Lu HF, Chen YL, Yang JS, Yang YY, Liu JY, Hsu SC et al (2010) Antitumor activity of capsaicin on human colon cancer cells in vitro and colo 205 tumor xenografts in vivo. J Agric Food Chem 58:12999–13005

    CAS  PubMed  Google Scholar 

  • Llovet JM, Bruix J (2008) Molecular targeted therapies in hepatocellular carcinoma. Hepatology 48:1312–1327

    CAS  PubMed Central  PubMed  Google Scholar 

  • Macho A, Calzado MA, Munoz-Blanco J, Gomez-Diaz C, Gajate C, Mollinedo F et al (1999) Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium. Cell Death Differ 6:155–165

    CAS  PubMed  Google Scholar 

  • Macho A, Sancho R, Minassi A, Appendino G, Lawen A, Munoz E (2003) Involvement of reactive oxygen species in capsaicinoid-induced apoptosis in transformed cells. Free Radic Res 37:611–619

    CAS  PubMed  Google Scholar 

  • Maity R, Sharma J, Jana NR (2010) Capsaicin induces apoptosis through ubiquitin-proteasome system dysfunction. J Cell Biochem 109:933–942

    CAS  PubMed  Google Scholar 

  • Malagarie-Cazenave S, Olea-Herrero N, Vara D, Diaz-Laviada I (2009) Capsaicin, a component of red peppers, induces expression of androgen receptor via PI3 K and MAPK pathways in prostate LNCaP cells. FEBS Lett 583:141–147

    CAS  PubMed  Google Scholar 

  • Mao LC, Wang HM, Lin YY, Chang TK, Hsin YH, Chueh PJ (2008) Stress-induced down-regulation of tumor-associated NADH oxidase during apoptosis in transformed cells. FEBS Lett 582:3445–3450

    CAS  PubMed  Google Scholar 

  • Matsuda A, Machii R (2013) Worldwide relative burden of cancer death in 2008 extrapolated from the WHO mortality database. Jpn J Clin Oncol 43:102

    PubMed  Google Scholar 

  • Moon DO, Kang CH, Kang SH, Choi YH, Hyun JW, Chang WY et al (2012) Capsaicin sensitizes TRAIL-induced apoptosis through Sp1-mediated DR5 up-regulation: involvement of Ca(2+) influx. Toxicol Appl Pharmacol 259:87–95

    CAS  PubMed  Google Scholar 

  • Mori A, Lehmann S, O’Kelly J, Kumagai T, Desmond JC, Pervan M et al (2006) Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res 66:3222–3229

    CAS  PubMed  Google Scholar 

  • Morre DJ, Caldwell S, Mayorga A, Wu LY, Morre DM (1997) NADH oxidase activity from sera altered by capsaicin is widely distributed among cancer patients. Arch Biochem Biophys 342:224–230

    CAS  PubMed  Google Scholar 

  • 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 92:1831–1835

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morre DJ, Hostetler B, Weston N, Kim C, Morre DM (2008) Cancer type-specific tNOX isoforms: a putative family of redox protein splice variants with cancer diagnostic and prognostic potential. BioFactors 34:201–207

    PubMed  Google Scholar 

  • Morre DJ, Sun E, Geilen C, Wu LY, de Cabo R, Krasagakis K et al (1996) Capsaicin inhibits plasma membrane NADH oxidase and growth of human and mouse melanoma lines. Eur J Cancer 32A:1995–2003

    CAS  PubMed  Google Scholar 

  • Mueller M, Beck V, Jungbauer A (2011) PPAR alpha activation by culinary herbs and spices. Planta Med 77:497–504

    CAS  PubMed  Google Scholar 

  • O’Neill J, Brock C, Olesen AE, Andresen T, Nilsson M, Dickenson AH (2012) Unravelling the mystery of capsaicin: a tool to understand and treat pain. Pharmacol Rev 64:939–971

    PubMed Central  PubMed  Google Scholar 

  • Oh SH, Kim YS, Lim SC, Hou YF, Chang IY, You HJ (2008) Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces autophagy in human cancer cells in a catalase-regulated manner. Autophagy 4:1009–1019

    CAS  PubMed  Google Scholar 

  • Popovich DG, Tiaras F, Yeo CR, Zhang W (2010) Lovastatin interacts with natural products to influence cultured hepatocarcinoma cell (hep-g2) growth. J Am Coll Nutr 29:204–210

    CAS  PubMed  Google Scholar 

  • 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:e20151

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pramanik KC, Srivastava SK (2012) Apoptosis signal-regulating kinase 1-thioredoxin complex dissociation by capsaicin causes pancreatic tumor growth suppression by inducing apoptosis. Antioxid Redox Signal 17:1417–1432

    CAS  PubMed Central  PubMed  Google Scholar 

  • Prescott ED, Julius D (2003) A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300:1284–1288

    CAS  PubMed  Google Scholar 

  • Quaglia A, Lillini R, Crocetti E, Buzzoni C, and Vercelli M (2013) Incidence and mortality trends for four major cancers in the elderly and middle-aged adults: an international comparison. Surg Oncol 22(2):e31–e38

    Google Scholar 

  • Rajput S, Mandal M (2012) Antitumor promoting potential of selected phytochemicals derived from spices: a review. Eur J Cancer Prev 21:205–215

    CAS  PubMed  Google Scholar 

  • Reilly CA, Ehlhardt WJ, Jackson DA, Kulanthaivel P, Mutlib AE, Espina RJ et al (2003) Metabolism of capsaicin by cytochrome P450 produces novel dehydrogenated metabolites and decreases cytotoxicity to lung and liver cells. Chem Res Toxicol 16:336–349

    CAS  PubMed  Google Scholar 

  • Reilly CA, Henion F, Bugni TS, Ethirajan M, Stockmann C, Pramanik KC et al (2013) Reactive intermediates produced from the metabolism of the vanilloid ring of capsaicinoids by P450 enzymes. Chem Res Toxicol 26(1):55–66

    Google Scholar 

  • Rychkov GY, Barritt GJ (2011) Expression and function of TRP channels in liver cells. Adv Exp Med Biol 704:667–686

    CAS  PubMed  Google Scholar 

  • 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 12:2013–2024

    CAS  PubMed  Google Scholar 

  • Sanchez AM, Martinez-Botas J, Malagarie-Cazenave S, Olea N, Vara D, Lasuncion MA et al (2008) Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: a microarray study. Biochem Biophys Res Commun 372:785–791

    CAS  PubMed  Google Scholar 

  • 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 11:89–99

    CAS  PubMed  Google Scholar 

  • Sanchez MG, Sanchez AM, Collado B, Malagarie-Cazenave S, Olea N, Carmena MJ et al (2005) Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue. Eur J Pharmacol 515:20–27

    CAS  PubMed  Google Scholar 

  • Santoni G, Caprodossi S, Farfariello V, Liberati S, Gismondi A, Amantini C (2012) Antioncogenic effects of transient receptor potential vanilloid 1 in the progression of transitional urothelial cancer of human bladder. ISRN Urol 2012:458238

    PubMed Central  PubMed  Google Scholar 

  • Schulze A, Harris AL (2012) How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature 491:364–373

    CAS  PubMed  Google Scholar 

  • Schwartz L, Guais A, Israel M, Junod B, Steyaert JM, Crespi E et al (2013) Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin. Invest New Drugs 31:256–264

    CAS  PubMed  Google Scholar 

  • Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T et al (2012) Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 62:220–241

    PubMed  Google Scholar 

  • Singh S, Natarajan K, Aggarwal BB (1996) Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a potent inhibitor of nuclear transcription factor-kappa B activation by diverse agents. J Immunol 157:4412–4420

    CAS  PubMed  Google Scholar 

  • Sinha K, Das J, Pal PB, Sil PC (2013) Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol 87(7):1157–1180

    Google Scholar 

  • Stone KR, Mickey DD, Wunderli H, Mickey GH, Paulson DF (1978) Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer 21:274–281

    CAS  PubMed  Google Scholar 

  • Sung B, Prasad S, Ravindran J, Yadav VR, Aggarwal BB (2012) Capsazepine, a TRPV1 antagonist, sensitizes colorectal cancer cells to apoptosis by TRAIL through ROS-JNK-CHOP-mediated upregulation of death receptors. Free Radic Biol Med 53:1977–1987

    CAS  PubMed Central  PubMed  Google Scholar 

  • Suresh D, Srinivasan K (2010) Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats. Indian J Med Res 131:682–691

    CAS  PubMed  Google Scholar 

  • Surh YJ (2002) More than spice: capsaicin in hot chili peppers makes tumor cells commit suicide. J Natl Cancer Inst 94:1263–1265

    CAS  PubMed  Google Scholar 

  • Surh YJ, Lee SS (1995) Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential. Life Sci 56:1845–1855

    CAS  PubMed  Google Scholar 

  • Tamburrino A, Piro G, Carbone C, Tortora G, Melisi D (2013) Mechanisms of resistance to chemotherapeutic and anti-angiogenic drugs as novel targets for pancreatic cancer therapy. Front Pharmacol 4:56

    PubMed Central  PubMed  Google Scholar 

  • Thoennissen NH, O’Kelly J, Lu D, Iwanski GB, La DT, Abbassi S et al (2010) Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR/HER-2 pathway. Oncogene 29:285–296

    CAS  PubMed  Google Scholar 

  • Tsou MF, Lu HF, Chen SC, Wu LT, Chen YS, Kuo HM et al (2006) Involvement of Bax, Bcl-2, Ca2+ and caspase-3 in capsaicin-induced apoptosis of human leukemia HL-60 cells. Anticancer Res 26:1965–1971

    CAS  PubMed  Google Scholar 

  • Vaiopoulos AG, Athanasoula KC, Papavassiliou AG (2013) NF-kappaB in colorectal cancer. J Mol Med (Berl) 91(9):1029–1037

    Google Scholar 

  • Vercelli C, Barbero R, Cuniberti B, Odore R, Re G (2013) Expression and functionality of TRPV1 receptor in human MCF-7 and canine CF.41 cells. Vet Comp Oncol. doi:10.1111/vco.12028 [Epub ahead of print]

  • Vickers AJ, Ulmert D, Sjoberg DD, Bennette CJ, Bjork T, Gerdtsson A et al (2013) Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40–55 and long term risk of metastasis: case-control study. BMJ 346:f2023

    PubMed Central  PubMed  Google Scholar 

  • Vriens J, Janssens A, Prenen J, Nilius B, Wondergem R (2004) TRPV channels and modulation by hepatocyte growth factor/scatter factor in human hepatoblastoma (HepG2) cells. Cell Calcium 36:19–28

    CAS  PubMed  Google Scholar 

  • Wahyuni Y, Ballester AR, Sudarmonowati E, Bino RJ, Bovy AG (2013) Secondary metabolites of capsicum species and their importance in the human diet. J Nat Prod 76(4):783–793

    Google Scholar 

  • Walpole CS, Bevan S, Bloomfield G, Breckenridge R, James IF, Ritchie T et al (1996) Similarities and differences in the structure-activity relationships of capsaicin and resiniferatoxin analogues. J Med Chem 39:2939–2952

    CAS  PubMed  Google Scholar 

  • Walpole CS, Wrigglesworth R, Bevan S, Campbell EA, Dray A, James IF et al (1993) Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain “C-region”. J Med Chem 36:2381–2389

    CAS  PubMed  Google Scholar 

  • Wang G, Yang ZQ, Zhang K (2010) Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential. Am J Transl Res 2:65–74

    PubMed Central  PubMed  Google Scholar 

  • Wang HM, Chueh PJ, Chang SP, Yang CL, Shao KN (2008) Effect of Ccapsaicin on tNOX (ENOX2) protein expression in stomach cancer cells. BioFactors 34:209–217

    PubMed  Google Scholar 

  • Ward PS, Thompson CB (2012) Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell 21:297–308

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wolvetang EJ, Larm JA, Moutsoulas P, Lawen A (1996) Apoptosis induced by inhibitors of the plasma membrane NADH-oxidase involves Bcl-2 and calcineurin. Cell Growth Differ 7:1315–1325

    CAS  PubMed  Google Scholar 

  • Yang J, Luo B, Xu G, Li T, Chen Y, 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

    Google Scholar 

  • 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 75:735–741

    PubMed  Google Scholar 

  • Yessoufou A, Wahli W (2010) Multifaceted roles of peroxisome proliferator-activated receptors (PPARs) at the cellular and whole organism levels. Swiss Med Wkly 140:w13071

    CAS  PubMed  Google Scholar 

  • Yoon JH, Ahn SG, Lee BH, Jung SH, Oh SH (2012) Role of autophagy in chemoresistance: regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNA-PKcs and PARP-1. Biochem Pharmacol 83:747–757

    CAS  PubMed  Google Scholar 

  • Yoshitani SI, Tanaka T, Kohno H, Takashima S (2001) Chemoprevention of azoxymethane-induced rat colon carcinogenesis by dietary capsaicin and rotenone. Int J Oncol 19:929–939

    CAS  PubMed  Google Scholar 

  • Youssef J, Badr M (2011) Peroxisome proliferator-activated receptors and cancer challenges and opportunities. Br J Pharmacol 164(1):68–82

    Google Scholar 

  • Zhai XJ, Chen JG, Liu JM, Shi F, Lu YN (2013) Food-drug interactions: effect of capsaicin on the pharmacokinetics of simvastatin and its active metabolite in rats. Food Chem Toxicol 53:168–173

    CAS  PubMed  Google Scholar 

  • Zhang J, Nagasaki M, Tanaka Y, Morikawa S (2003) Capsaicin inhibits growth of adult T-cell leukemia cells. Leuk Res 27:275–283

    CAS  PubMed  Google Scholar 

  • Zhang JH, Lai FJ, Chen H, Luo J, Zhang RY, Bu HQ et al (2013) Involvement of the phosphoinositide 3-kinase/Akt pathway in apoptosis induced by capsaicin in the human pancreatic cancer cell line PANC-1. Oncol Lett 5:43–48

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang QH, Hu JP, Wang BL, Li Y (2012) Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res 14:382–395

    CAS  PubMed  Google Scholar 

  • 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 13:1465–1478

    CAS  PubMed  Google Scholar 

  • Zhu Y, Qi C, Korenberg JR, Chen XN, Noya D, Rao MS et al (1995) Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms. Proc Natl Acad Sci U S A 92:7921–7925

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work has been supported by Spanish Minneco (grant BFU2012-31444), Comunidad de Madrid (Grant S2010/BMD-2308), and Fundación Tatiana Pérez de Guzmán.

Author information

Authors and Affiliations

  1. Biochemistry and Molecular Biology Unit, Department of System Biology, University of Alcala, 28871, Madrid, Spain

    Inés Díaz-Laviada & Nieves Rodríguez-Henche

Authors
  1. Inés Díaz-Laviada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nieves Rodríguez-Henche
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Inés Díaz-Laviada .

Editor information

Editors and Affiliations

  1. Department of Toxicology and Narcotics, National Research Center, Cairo, Egypt

    Omar M. E. Abdel-Salam

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Basel

About this chapter

Cite this chapter

Díaz-Laviada, I., Rodríguez-Henche, N. (2014). The Potential Antitumor Effects of Capsaicin. In: Abdel-Salam, O. (eds) Capsaicin as a Therapeutic Molecule. Progress in Drug Research, vol 68. Springer, Basel. https://doi.org/10.1007/978-3-0348-0828-6_8

Download citation

Publish with us

Policies and ethics

Search

Navigation