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G2/M cell cycle arrest and induction of apoptosis by a stilbenoid, 3,4,5-trimethoxy-4′-bromo-cis-stilbene, in human lung cancer cells

Title
G2/M cell cycle arrest and induction of apoptosis by a stilbenoid, 3,4,5-trimethoxy-4′-bromo-cis-stilbene, in human lung cancer cells
Authors
Lee E.-J.Min H.-Y.Joo Park H.Chung H.-J.Kim S.Nam Han Y.Lee S.K.
Ewha Authors
이상국
Issue Date
2004
Journal Title
Life Sciences
ISSN
0024-3205JCR Link
Citation
Life Sciences vol. 75, no. 23, pp. 2829 - 2839
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Stilbenoids, including resveratrol (3,5,4′-trihydroxy-trans-stilbene) which is a naturally occurring phytoalexin abundant in grapes and several plants, have been shown to be active in inhibiting proliferation and inducing apoptosis in human cancer cell lines. Using resveratrol as the prototype, we have synthesized various analogs and evaluated their growth inhibitory effects in cultured human cancer cells. In the present study, we show that one of the stilbenoids, 3,4,5-trimethoxy-4′-bromo-cis-stilbene (BCS), was more effective than its corresponding trans-isomer and resveratrol on the inhibition of cancer cell growth. Prompted by the strong growth inhibitory activity of BCS (IC 50; 0.03 μM) compared to its trans-isomer (IC 50; 6.36 μM) and resveratrol (IC 50; 33.0 μM) in cultured human lung cancer cells (A549), we investigated its mechanism of action. BCS induced arrest at the G2/M phase cell cycle in the early time and subsequently increased in the sub-G1 phase DNA contents in a time-dependent manner, indicating induction of apoptosis. Morphological observation with round-up shape and DNA fragmentation was also revealed the apoptotic phenomena. BCS treatment elevated the expression levels of the pro-apoptotic protein p53, the cyclin-dependent kinase inhibitor p21, and the release of cytochrome c in the cytosol. The down-regulation of checkpoint protein cyclin B1 by BCS was well correlated with the cell cycle arrest at G2/M. These data suggest the potential of BCS to serve as a cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell cycle and induction of apoptosis of human lung cancer cells. © 2004 Elsevier Inc. All rights reserved.
DOI
10.1016/j.lfs.2004.07.002
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약학대학 > 약학과 > Journal papers
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