Cytotoxicity and genotoxicity of capsaicin in human neuroblastoma cells SHSY-5Y.
Capsaicin, a natural product of Capsicum species, induces excitation of pain perception at nociceptive terminals. Our previous studies have shown that capsaicin inhibits protein synthesis in cultured monkey kidneys cells (Vero cells) and in primoculture of rat astrocytes. We have now investigated the effect of capsaicin on human neuroblastoma cells SHSY-5Y. The cytotoxicity has been assessed by incorporation of [(3)H]L-leucine into cellular protein in the presence of capsaicin and the genotoxicity has been evaluated using the comet assay and the fragmentation assay after incubation of neuroblastoma cells with 25-100 microM capsaicin. The concentration required to inhibit 50% of the protein synthesis (IC(50)) was found to be 60 microM after incubation with the toxin during one cellular cycle (5 days) of SHSY-5Y. The results of the comet test and DNA fragmentation assay clearly suggest that capsaicin is able to induce DNA strand breaks already with concentrations in the range of 50 microM, corresponding to 29.3 microM of capsaicin not bound to alpha-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 quantity applied). Because DNA strand breaks or DNA lesions may affect cellular functions, lead to cell death and/or mutagenesis, our data in case of inappropriate DNA repair may have important implications for the possible health threats of capsaicin, specially in the case of misuse of capsaicin preparations in pathological situations.
Richeux
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Laboratory of Toxicology and Applied Hygiene, Faculty of Pharmaceutical Sciences, University of Bordeaux 2 Victor Segalen, 146 rue Léo Saignat, F-33076 Bordeaux, France.
Cascante
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Ennamany
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Saboureau
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Creppy
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D002211:Capsaicin / Q000737:chemistry / Q000633:toxicity*; D002452:Cell Count; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects*; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000633:toxicity; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D004273:DNA, Neoplasm; D011500:Protein Synthesis Inhibitors; D002211:Capsaicin