title: Capsaicin-Induced Death of Human Haematological Malignant Cell Lines Is Independent of TRPV1 Activation.
abstract: 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.
authors.affiliation: School of Health Sciences, University of Tasmania, Launceston, Australia.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Omari
authors.forename: Murray J
authors.initials: MJ
authors.lastname: Adams
authors.forename: Dale A
authors.initials: DA
authors.lastname: Kunde
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Geraghty
mesh_terms: D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D019337:Hematologic Neoplasms / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D010078:Oxazines / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D014966:Xanthenes / Q000378:metabolism
chemical_list: D063387:Cannabinoid Receptor Antagonists; D007211:Indoles; D010078:Oxazines; D010880:Piperidines; D011720:Pyrazoles; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D014966:Xanthenes; C005843:resazurin; C103505:AM 251; D002211:Capsaicin; C094023:iodopravadoline