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学科主题: 药学
题名:
Cell growth inhibition, G(2)M cell cycle arrest, and apoptosis induced by the novel compound Alternol in human gastric carcinoma cell line MGC803
作者: 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
发表日期: 2007-12-01
DOI: 10.1007/s10637-007-9057-4
卷: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57163
Appears in Collections:北京大学药学院_分子与细胞药理学系_期刊论文

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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

Recommended Citation:
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.
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