Chemical and Cytotoxic Constituents from the Leaves of Cinnamomum kotoense

摘要

Three new butanolides,kotomolide A(1),isokotomolide A(2),and kotomolide B(3),and a new secobutanolide,secokotomolide A(4),along with 21 known compounds were isolated from the leaves of Cinnamomum kotoense.Their structures were determined by spectroscopic analyses.Compound 4 was found to induce significant cell death in the human HeLa cell line.Apoptotic-related DNA damage can be positively related to the dose of compound 4.The DNA damage was measured by the percentage of subG1(24 h after the treatment of compound 4)as determined by cell cycle analysis and TUNEL assay.Treatment with 4 significantly increased intracellular H_2O_2 and/or peroxide,nitric oxide(NO)at 1,3,and 24 h.Our results also showed that compound 4 induced(a)noticeable reduction of mitochondrial transmembrane potential(DELTA PSI_m),(b)activation of caspase 3/7,and(c)up-regulation of the p53 expression.Compound 4-induced DNA damage was found to markedly decrease when the cells were pretreated with an intracellular glutathione supplement(glutathione ethyl ester).These results suggest that an increase of H_2O_2 and/or peroxide by compound 4 is the initial apoptotic event.The intracellular GSH depletion is a critical event in compound 4-induced apoptosis in HeLa cells.