Inhibition of Human Haematological Malignant Cell Lines by Capsaicin is not TRPV1-Mediated

Aim: Transient receptor potential vanilloid-1 (TRPV1) is a non-selective cation channel activated by a variety of endogenous and exogenous stimuli, including the major active component of ‘hot chilli peppers’, capsaicin. Recent evidence suggests that capsaicin induces apoptosis and inhibits cell proliferation, although this has not been extensively investigated in haematological malignancies. The aims of this study were to: 1) investigate the whether capsaicin kills human haematological malignant cells, and if so, 2) whether this action was TRPV1-mediated. Methods: THP-1 (acute monocytic leukaemia), U266B1 (myeloma) and U937 (histiocytic lymphoma) cells were exposed to increasing concentrations of capsaicin (8-1000 µM) in the presence and absence of TRPV1, and cannabinoid 1 and 2 receptor (CB1, CB2; 0.1-100 µM) antagonists. Cell metabolic activity (indicative of viability) was measured after 24hrs using the alamarBlue® method (resazurin reduction assay). Results: Capsaicin reduced viable THP-1, U266B1 and U937 cell numbers in a concentration-dependant manner. A biphasic effect was observed on THP-1 cells [EC50 and IC50(95% CI) = 32.9(19.9-54.3) and 219(144-246) µM]. SB452533 and AM251 (100 µM) suppressed the capsaicin-induced increase in THP-1 cell activity (P<0.001). U266B1 cells were more resistant to capsaicin than THP-1 and U937 cells. Cell activity was significantly inhibited by capsaicin in U937 compared to U266 cells (IC50: 197 vs. 431 µM, respectively, P<0.008). AM251 and SB452533 appeared to act as partial agonists and displayed a synergistic effect with capsaicin in U937 cells. Conclusion: THP-1, U266B1 and U937 cells responded differently to capsaicin. TRPV1, CB1 and CB2 antagonists did not affect capsaicin-induced changes in U266B1 cell activity although CB1 and CB2 receptors appeared to mediate an increase in cell activity in THP-1. We conclude that capsaicin inhibits the viability of haematological malignant cells through a non-TRPV1-dependent mechanism.