Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro
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Yu-Tang Chin1,*, Meng-Ti Hsieh1,*, Sheng-Huei Yang2, Po-Wei Tsai3, Shwu-Huey Wang4, Ching-Chiung Wang3, Yee-Shin Lee2, Guei-Yun Cheng1, Wei-Chun HuangFu1,2, David London5, Heng-Yuan Tang5, Earl Fu6, Yun Yen2,7, Leroy F. Liu1, Hung-Yun Lin1,2, Paul J. Davis5,8
1Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan
2PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
3School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
4Core Facility, Taipei Medical University, Taipei, Taiwan
5Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA
6Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan
7Department of Molecular Pharmacology, City of Hope National Medical Center and Beckman Research Center, Duarte, California, USA
8Albany Medical College, Albany, New York, USA
*These authors contributed equally to this work
Hung-Yun Lin, e-mail: [email protected]
Keywords: stilbene, integrin αvβ3, apoptosis, anti-proliferation, breast cancer
Received: July 21, 2014 Accepted: October 23, 2014 Published: November 08, 2014
We have used a perfusion bellows cell culture system to investigate resveratrolinduced 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 μM) 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 μM resveratrol for 4 h daily × 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 pro-apoptotic 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 αvβ3.
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