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.

1.
Monsereenusorn Y, Kongsamut S, Pezalla PD: Capsaicin - a literature survey. Crit Rev Toxicol 1982;10:321-339.
2.
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.
3.
Alexander SPH, Mathie A, Peters JA: Ion channels. Br J Pharmacol 2007;150:S96-S121.
4.
Ramsey IS, Delling M, Clapham DE: An introduction to TRP channels. Annu Rev Physiol 2006;68:619-647.
5.
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.
6.
Fernandes ES, Fernandes MA, Keeble JE: The functions of TRPA1 and TRPV1: moving away from sensory nerves. Br J Pharmacol 2012;166:510-521.
7.
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.
8.
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.
9.
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.
10.
Hail N Jr, Lotan R: Examining the role of mitochondrial respiration in vanilloid-induced apoptosis. J Natl Cancer Inst 2002;94:1281-1292.
11.
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.
12.
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.
13.
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.
14.
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.
15.
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.
16.
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.
17.
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.
18.
Preta G, Fadeel B: Scythe cleavage during Fas (APO-1)-and staurosporine-mediated apoptosis. FEBS Lett 2012;586:747-752.
19.
Chen Y, Buck J: Cannabinoids protect cells from oxidative cell death: a receptor-independent mechanism. J Pharmacol Exp Ther 2000;293:807-812.
20.
Pertwee RG: The pharmacology of cannabinoid receptors and their ligands: an overview. Int J Obes (Lond) 2006;30(suppl 1):S13-S18.
21.
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.
22.
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.
23.
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.
24.
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.
25.
Pisanti S, Bifulco M: Endocannabinoid system modulation in cancer biology and therapy. Pharmacol Res 2009;60:107-116.
26.
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.
27.
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.
28.
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.
29.
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.
30.
Zhivotovsky B, Orrenius S: Calcium and cell death mechanisms: a perspective from the cell death community. Cell Calcium 2011;50:211-221.
31.
Lee YS, Nam DH, Kim JA: Induction of apoptosis by capsaicin in A172 human glioblastoma cells. Cancer Lett 2000;161:121-130.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.