The effect of the plant-derived vanilloid, capsaicin (CAP), on the metabolic activity of THP-1, U266B1 and U937 hematological malignancy cells was determined. CAP reduced metabolic activity in a concentration-dependent manner in the three cell lines. A biphasic effect was observed on THP-1 cells (EC50: IC50 (95% CI) 32.9 (19.9-54.3)/219 (144-246) µmol/l). U266B1 cells were more resistant to CAP than THP-1 and U937. Metabolic activity was significantly inhibited by CAP in U937 compared to U266B1 cells (IC50: 197 versus 431 µmol/l, respectively, p < 0.008). Transient receptor potential vanilloid-1 (TRPV1) and CB1 antagonists (SB452533 and AM251, respectively) suppressed the CAP-induced increase in THP-1 cell metabolic activity (p < 0.001). AM251 and SB452533 appeared to act as partial agonists and displayed a synergistic effect with CAP in U937 cells. CAP inhibits the metabolic activity of malignant hematological cells through non-TRPV1-dependent mechanisms.

Monsereenusorn Y, Kongsamut S, Pezalla PD: Capsaicin - a literature survey. Crit Rev Toxicol 1982;10:321-339.
Nagy I, Santha P, Jancso G, Urban L: The role of the vanilloid (capsaicin) receptor (TRPV1) in physiology and pathology. Eur J Pharmacol 2004;500:351-369.
Alexander SPH, Mathie A, Peters JA: Ion channels. Br J Pharmacol 2007;150:S96-S121.
Ramsey IS, Delling M, Clapham DE: An introduction to TRP channels. Annu Rev Physiol 2006;68:619-647.
Roberts JC, Davis JB, Benham CD: [3H]Resiniferatoxin autoradiography in the CNS of wild-type and TRPV1 null mice defines TRPV1 (VR-1) protein distribution. Brain Res 2004;995:176-183.
Fernandes ES, Fernandes MA, Keeble JE: The functions of TRPA1 and TRPV1: moving away from sensory nerves. Br J Pharmacol 2012;166:510-521.
Saunders CI, Fassett RG, Geraghty DP: Up-regulation of TRPV1 in mononuclear cells of end-stage kidney disease patients increases susceptibility to N-arachidonoyl-dopamine (NADA)-induced cell death. Biochim Biophys Acta 2009;1792:1019-1026.
Saunders CI, Kunde DA, Crawford A, Geraghty DP: Expression of transient receptor potential vanilloid 1 (TRPV1) and 2 (TRPV2) in human peripheral blood. Mol Immunol 2007;44:1429-1435.
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;102:977-990.
Hail N Jr, Lotan R: Examining the role of mitochondrial respiration in vanilloid-induced apoptosis. J Natl Cancer Inst 2002;94:1281-1292.
Contassot E, Tenan M, Schnüriger V, Pelte MF, Dietrich PY: Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1. Gynecol Oncol 2004;93:182-188.
Amantini C, Ballarini P, Caprodossi S, Nabissi M, Morelli MB, Lucciarini R, et al: 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 2009;30:1320-1329.
Chen D, Yang Z, Wang Y, Zhu G, Wang X: Capsaicin induces cycle arrest by inhibiting cyclin-dependent-kinase in bladder carcinoma cells. Int J Urol 2012;19:662-668.
Cao S, Chen H, Xiang S, Hong J, Weng L, Zhu H, et al: Anti-cancer effects and mechanisms of capsaicin in chili peppers. Am J Plant Sci 2015;6:3075-3081.
Macho A, Calzado MA, Munoz-Blanco J, Gomez-Diaz C, Gajate C, Mollinedo F, et al: Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium. Cell Death Differ 1999;6:155-165.
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;64:1071-1078.
Bhutani M, Pathak AK, Nair AS, Kunnumakkara AB, Guha S, Sethi G, et al: Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation. Clin Cancer Res 2007;13:3024-3032.
Preta G, Fadeel B: Scythe cleavage during Fas (APO-1)-and staurosporine-mediated apoptosis. FEBS Lett 2012;586:747-752.
Chen Y, Buck J: Cannabinoids protect cells from oxidative cell death: a receptor-independent mechanism. J Pharmacol Exp Ther 2000;293:807-812.
Pertwee RG: The pharmacology of cannabinoid receptors and their ligands: an overview. Int J Obes (Lond) 2006;30(suppl 1):S13-S18.
Reilly CA, Johansen ME, Lanza DL, Lee J, Lim JO, Yost GS: Calcium-dependent and independent mechanisms of capsaicin receptor (TRPV1)-mediated cytokine production and cell death in human bronchial epithelial cells. J Biochem Mol Toxicol 2005;19:266-275.
Johansen ME, Reilly CA, Yost GS: TRPV1 antagonists elevate cell surface populations of receptor protein and exacerbate TRPV1-mediated toxicities in human lung epithelial cells. Toxicol Sci 2006;89:278-286.
Sarker KP, Maruyama I: Anandamide induces cell death independently of cannabinoid receptors or vanilloid receptor 1: possible involvement of lipid rafts. Cell Mol Life Sci 2003;60:1200-1208.
Ziglioli F, Frattini A, Maestroni U, Dinale F, Ciufifeda M, Cortellini P: Vanilloid-mediated apoptosis in prostate cancer cells through a TRPV-1 dependent and a TRPV-1-independent mechanism. Acta Biomed 2009;80:13-20.
Pisanti S, Bifulco M: Endocannabinoid system modulation in cancer biology and therapy. Pharmacol Res 2009;60:107-116.
Kim JY, Kim EH, Kim SU, Kwon TK, Choi KS: Capsaicin sensitizes malignant glioma cells to TRAIL-mediated apoptosis via DR5 upregulation and survivin downregulation. Carcinogenesis 2010;31:367-375.
Amantini C, Mosca M, Lucciarini R, Perfumi M, Morrone S, Piccoli M, et al: Distinct thymocyte subsets express the vanilloid receptor VR1 that mediates capsaicin-induced apoptotic cell death. Cell Death Differ 2004;11:1342-1356.
Ito N, Ruegg UT, Kudo A, Miyagoe-Suzuki Y, Takeda S: Capsaicin mimics mechanical load-induced intracellular signaling events: involvement of TRPV1-mediated calcium signaling in induction of skeletal muscle hypertrophy. Channels (Austin) 2013;7:221-224.
Dedov VN, Mandadi S, Armati PJ, Verkhratsky A: Capsaicin-induced depolarisation of mitochondria in dorsal root ganglion neurons is enhanced by vanilloid receptors. Neuroscience 2001;103:219-226.
Zhivotovsky B, Orrenius S: Calcium and cell death mechanisms: a perspective from the cell death community. Cell Calcium 2011;50:211-221.
Lee YS, Nam DH, Kim JA: Induction of apoptosis by capsaicin in A172 human glioblastoma cells. Cancer Lett 2000;161:121-130.
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