title: Apoptosis induction by dohevanil, a DHA substitutive analog of capsaicin, in MCF-7 cells.
abstract: Capsaicin (8-methyl-N-vanillyl-6-nonenamide), a major pungent ingredient in a variety of red peppers of the genus Capsicum, is a type of vanilloid. It has been shown to induce apoptosis in many cell types. The effects of vanilloids on apoptosis induction are thought to be correlated with the length and degree of the unsaturation of the fatty acyl chains. In this study, we compared the effect of capsaicin and its docosahexaenoic acid (DHA, C22:6) analog (we named as dohevanil) on human breast cancer MCF-7 cells, which do not express caspase-3. Dohevanil, which was synthesized from DHA and vanillylamine, has longer and highly unsaturated fatty acyl chain than capsaicin. We showed that both vanilloids exhibit effects of growth inhibition and DNA fragmentation induction in MCF-7 cells. These effects of dohevanil were more potent than capsaicin. Because these effects were inhibited by z-VAD-fmk, a broad-spectrum caspase inhibitor, the vanilloids induced the apoptosis via caspase-dependent pathway not involving caspase-3. In conclusion, dohevanil has a more potent effect on apoptosis induction in MCF-7 cells than capsaicin.
authors.affiliation: Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan.
authors.lastname: Tuoya
authors.forename: Naomichi
authors.initials: N
authors.lastname: Baba
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shimoishi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Murata
authors.forename: Mikiro
authors.initials: M
authors.lastname: Tada
authors.forename: Masamichi
authors.initials: M
authors.lastname: Koseki
authors.forename: Kyoya
authors.initials: K
authors.lastname: Takahata
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C509406:dohevanil; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002211:Capsaicin