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Cell growth inhibition, G(2)M cell cycle arrest, and apoptosis induced by the novel compound Alternol in human gastric carcinoma cell line MGC803
Liu, Xia; Wang, Jingze; Sun, Bo; Zhang, Yajing; Zhu, Jin; Li, Changling
关键词Alternol g(2)m Arrest Apoptosis Cdc2 Cdc25c Wee1 Plk1
刊名INVESTIGATIONAL NEW DRUGS
2007-12-01
DOI10.1007/s10637-007-9057-4
25期:6页:505-517
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Pharmacology & Pharmacy
研究领域[WOS]Oncology ; Pharmacology & Pharmacy
关键词[WOS]DNA-DAMAGE CHECKPOINT ; PROTEIN-KINASE ; ANTINEOPLASTIC AGENT ; CDC2 ; CANCER ; TAXOL ; P53 ; PHOSPHORYLATION ; DEGRADATION ; PACLITAXEL
英文摘要

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 G(2)M-related regulators. Our data show that Alternol inhibited the growth of MGC803 and induced G(2)M arrest. Coincident with G(2)M 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 G(2)M arrest because the elevated Caspase3, decreased MMP, and typical apoptotic morphology changes appeared after G(2)M arrest. These findings suggested that Alternol could inhibit the growth of MGC803 by inducing G(2)M 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.

语种英语
WOS记录号WOS:000249807800001
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57163
专题北京大学药学院_分子与细胞药理学系
作者单位1.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Pharmacol, Beijing 100083, Peoples R China
2.Chinese Acad Sci, Inst Zool, Natl Key Lab Biomembrane & Membrane Biotechnol, Beijing, Peoples R China
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GB/T 7714
Liu, Xia,Wang, Jingze,Sun, Bo,et al. Cell growth inhibition, G(2)M cell cycle arrest, and apoptosis induced by the novel compound Alternol in human gastric carcinoma cell line MGC803[J]. INVESTIGATIONAL NEW DRUGS,2007,25(6):505-517.
APA Liu, Xia,Wang, Jingze,Sun, Bo,Zhang, Yajing,Zhu, Jin,&Li, Changling.(2007).Cell growth inhibition, G(2)M cell cycle arrest, and apoptosis induced by the novel compound Alternol in human gastric carcinoma cell line MGC803.INVESTIGATIONAL NEW DRUGS,25(6),505-517.
MLA Liu, Xia,et al."Cell growth inhibition, G(2)M cell cycle arrest, and apoptosis induced by the novel compound Alternol in human gastric carcinoma cell line MGC803".INVESTIGATIONAL NEW DRUGS 25.6(2007):505-517.
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