[Show abstract][Hide abstract] ABSTRACT: Coleusin factor (CF), a kind of diterpenoids, is isolated and purified from the root of a Chinese tropical plant Coleus forskohlii by our laboratory. Our previous studies have demonstrated that CF significantly inhibits growth in some kinds of cancer cell lines. Here, we found that CF remarkably inhibited growth in human gastric cancer BGC-823 cells by decreasing cell proliferation, inducing G(0)/G(1) cell cycle arrest and apoptosis. CF also decreased the mitochondrial membrane potential in BGC-823 cells. Immunoblotting analysis revealed that CF significantly decreased the expressions of cyclinD1, Bcl-2, and Bcl-x(L), increased the expressions of cytosol cytochrome c, p53, p21, and Rb. In addition, CF significantly increased the expressions and activities of caspase-3 and -9. More importantly, CF potently inhibited the growth of BGC-823 cells xenografted in athymic nude mice with negligible body weight loss and damage towards the spleen. These results indicate that CF exerts a cytotoxic effect on BGC-823 cells by inducing cell cycle arrest and apoptosis.
[Show abstract][Hide abstract] ABSTRACT: Alternol is a novel compound purified from the fermenting products by microorganisms named as Alternaria alternata var. monosporus from the bark of Yew. In this study, we tested its effect on mouse lymphocyte leukemia L1210 cells. Alternol was found to inhibit the proliferation and induce apoptosis in L1210 cells. When the cells were treated with Alternol, chromatin condensation and phosphatidylserine externalization were observed with the down-regulation of the pro-survival gene Bcl-2 and the activation of caspase-3, caspase-9, but not caspase-8. Moreover, exposure of cells to Alternol resulted in a significant increase in reactive oxygen species (ROS) and mitochondrial transmembrane potential (DeltaPsim) depolarization. Taken together, these results demonstrate that Alternol is a potent agent in inducing L1210 cells to apoptosis, which involve caspase activation and ROS generation.
No preview · Article · Jan 2008 · Molecular and Cellular Biochemistry
[Show abstract][Hide abstract] ABSTRACT: Alternol is a novel compound purified from fermentation products of a microorganism in the bark of the yew tree. Because it has a similar origin as the anticancer agent paclitaxel, we hypothesized that Alternol may also have an anti-tumor effect. In this report, we chose human gastric carcinoma cell line MGC803 as the model to investigate the effects of Alternol. We evaluated cell viability using the CCK8 kit. The cell cycle distribution was analyzed by flow cytometry. AnnexinV combined with PI was performed to evaluate the apoptosis rate. The mitochondria membrane potential (MMP) was measured by a fluorescence-activated cell sorter using Rhodamin123 staining. We observed the morphological changes by immunofluorescence and Hochest33342 staining. RT-PCR and Western blot analysis were used to evaluate the changes of G2M-related regulators. Our data show that Alternol inhibited the growth of MGC803 and induced G2M arrest. Coincident with G2M arrest, phosphorylation of CDC2 on Tyr-15 was significantly elevated, which could be explained by the increase of Wee1 and decrease of CDC25C. The decreased expression of PLK1 may cause the elevation of Wee1 and CyclinB1 protein levels. Moreover, the apoptosis seemed to be secondary to G2M arrest because the elevated Caspase3, decreased MMP, and typical apoptotic morphology changes appeared after G2M arrest. These findings suggested that Alternol could inhibit the growth of MGC803 by inducing G2M arrest and apoptosis. We expected Alternol may be used as a lead compound one day and our experiments might provide some clues for further research.
No preview · Article · Jan 2008 · Investigational New Drugs