Cell growth inhibition, G2M cell cycle arrest, and apoptosis induced by the novel compound Alternol in human gastric carcinoma cell line MGC803.
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.
Liu
Xia
X
Department of Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083, People's Republic of China.
Wang
Jingze
J
Sun
Bo
B
Zhang
Yajing
Y
Zhu
Jin
J
Li
Changling
C
D000528:Alternaria; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice
C526095:Alternol; D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings