期刊
ONCOTARGET
卷 5, 期 24, 页码 12891-12907出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2632
关键词
stilbene; integrin alpha v beta 3; apoptosis; anti-proliferation; breast cancer
资金
- Taipei Medical University [TMU-102-AE1-B29]
- Ministry of Science and Technology Taiwan [MOST-102-2311-B-038-001]
- Department of Health (DOH) [MOHW103-TD-B-111-01]
- Taipei Medical University/Wang-Fan Hospital [102TMU-WFH-11]
We have used a perfusion bellows cell culture system to investigate resveratrol-induced anti-proliferation/apoptosis in a human estrogen receptor (ER)-negative breast cancer cell line (MDA-MB-231). Using an injection system to perfuse media with stilbene, we showed resveratrol (0.5 - 100 mu M) to decrease cell proliferation in a concentration-dependent manner. Comparison of influx and medium efflux resveratrol concentrations revealed rapid disappearance of the stilbene, consistent with cell uptake and metabolism of the agent reported by others. Exposure of cells to 10 mu M resveratrol for 4 h daily x 6 d inhibited cell proliferation by more than 60%. Variable extracellular acid-alkaline conditions (pH 6.8 - 8.6) affected basal cell proliferation rate, but did not alter anti-proliferation induced by resveratrol. Resveratrol-induced gene expression, including transcription of the most up-regulated genes and proapoptotic p53-dependent genes, was not affected by culture pH changes. The microarray findings in the context of induction of anti-proliferation with brief daily exposure of cells to resveratrol-and rapid disappearance of the compound in the perfusion system-are consistent with existence of an accessible initiation site for resveratrol actions on tumor cells, e. g., the cell surface receptor for resveratrol described on integrin alpha v beta 3.
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