Comparative effects of cinnamaldehyde and cinnamyl‐containing compounds on the viability of two human melanoma cell lines, SK‐MEL19 and SK‐MEL23 (LB611)

Abstract

Trans‐cinnamaldehyde (CA) is an α,β‐unsaturated carbonyl compound, derived from cinnamon, and contains a “Michael acceptor” functionality capable of alkylating nucleophilic residues. Such Michael acceptors are believed to interact with cellular nucleophiles through a Michael addition reaction, making them potential anticancer alkylating agents. Methyl trans‐cinnamyl ketone (MeK), methyl trans‐cinnamic ester (MeCE), and trans‐cinnamic acid (CAC) are cinnamyl‐containing compounds, and are structurally similar to CA, where they have the α,β‐unsaturated carbonyl moiety. This study investigated the effects of these cinnamyl‐containing compounds, alone and in the presence of 100µM glutathione (GSH) and/or 50µM ethacrynic acid (EA), compared to that of CA on human melanoma cell lines: SK‐MEL23 and SK‐MEL19. The viability of the cells was evaluated by MTS assay following 24h of incubation with the treatments. The results show that CA and MeCK exhibited a concentration‐dependent cytotoxicity, with MeCK being less cytotoxic. In the co‐treatment studies, the presence of GSH with the cinnamyl‐containing compounds did not provide protection to the cells, while co‐treatment of EA with the test compounds enhanced the cytotoxicity on the treated cells as compared to the control. In the combination treatment studies, the viability of the cells did not improve when GSH and EA were combined with the test compounds (triple combination) as compared to the co‐treatment of the test compounds with EA. These results indicate that CA was the most cytotoxic among the test compounds, and CAC caused the least cytotoxicity. The results suggest that both the reactivity of the “Michael acceptor” functionality and the lipophilicity of the cinnamyl‐containing compounds play a role in their cytotoxicity.Grant Funding Source: MCPHS Faculty Development Fund