Cytotoxicity and genotoxicity of capsaicin in human neuroblastoma cells SHSY-5Y

Capsaicin, a natural product of Capsicum species, induces excitation of pai n perception at nociceptive terminals. Our previous studies have shown that capsaicin inhibits protein synthesis in cultured monkey kidneys cells (Ver o cells) and in primoculture of rat astrocytes. We have now investigated th e effect of capsaicin on human neuroblastoma cells SHSY-5Y. The cytotoxicit y has been assessed by incorporation of [H-3]L-leucine into cellular protei n in the presence of capsaicin and the genotoxicity has been evaluated usin g the comet assay and the fragmentation assay after incubation of neuroblas toma cells with 25-100 mu M capsaicin. The concentration required to inhibi t 50% of the protein synthesis (IC50) was found to be 60 mu M after incubat ion with the toxin during one cellular cycle (5 days) of SHSY-5Y. The resul ts of the comet test and DNA fragmentation assay clearly suggest that capsa icin is able to induce DNA strand breaks already with concentrations in the range of 50 mu M, corresponding to 29.3 mu M of capsaicin not bound to alp ha-1 acid glycoprotein. Several daily topical applications of preparations containing 0.075% of capsaicin could lead to blood capsaicin concentration of this order of magnitude following transdermal passage (5% of the total q uantity applied). Because DNA strand breaks or DNA lesions may affect cellu lar functions, lead to cell death and/or mutagenesis, our data in case of i nappropriate DNA repair may have important implications for the possible he alth threats of capsaicin, specially in the case of misuse of capsaicin pre parations in pathological situations.