✍ Scribed by Jue Tu; Hong-Xiang Sun; Yi-Ping Ye
No coin nor oath required. For personal study only.
3b-Hydroxyolean-12-en-27-oic acid (1), a biologically active, pentacyclic triterpenoid isolated from the rhizomes of Astilbe chinensis, was found to be considerably more cytotoxic toward human colorectal carcinoma (COLO-205) and human cervical squamous carcinoma (HeLa) cells than its congener oleanolic acid (4). This suggests that the position of the COOH group significantly affects the cytotoxicity of oleanane-type pentacyclic triterpene carboxylic acids. To elucidate the underlying biological mechanism responsible for the cytotoxicity of 1, we investigated its growth-inhibitory effect on COLO-205 cells. Compound 1 induced a marked concentration-and time-dependent inhibition of cell proliferation, with the typical morphological characteristics of apoptosis, and under formation of DNA ladders in agarose-gel electrophoresis. Flow-cytometric analysis showed that the cell cycle of COLO-205 cells exposed to 1 was arrested in the G 0 /G 1 phase. Also, 1 increased and decreased the expression of Bax and Bcl-2 proteins, respectively, and lowered the mitochondrial transmembrane potential (Dy m ). The peptidic capase-3 inhibitor NH 2 -Asp-Glu-Val-Asp-CHO (at 1 mm) could increase the viability of COLO-205 cells previously treated with 1. These results indicate that 1 induces efficient cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering Dy m , and by activating the caspase-3 pathway.
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The title compound, C 30 H 48 O 3 ÁCH 4 O, is a cytotoxic and apoptosis-inducing triterpenoid which was isolated from the rhizome of Astilbe chinensis. The molecule is composed of ®ve six-membered rings. The cyclohexene ring adopts a slightly distorted half-chair conformation and the cyclohexane rin