title: Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro.
abstract: 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.
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Chin
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Meng-Ti
authors.initials: MT
authors.lastname: Hsieh
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Sheng-Huei
authors.initials: SH
authors.lastname: Yang
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Po-Wei
authors.initials: PW
authors.lastname: Tsai
authors.affiliation: Core Facility, Taipei Medical University, Taipei, Taiwan.
authors.forename: Shwu-Huey
authors.initials: SH
authors.lastname: Wang
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ching-Chiung
authors.initials: CC
authors.lastname: Wang
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Guei-Yun
authors.initials: GY
authors.lastname: Cheng
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan. PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: HuangFu
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: London
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Heng-Yuan
authors.initials: HY
authors.lastname: Tang
authors.affiliation: Department of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Earl
authors.initials: E
authors.lastname: Fu
authors.affiliation: PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Department of Molecular Pharmacology, City of Hope National Medical Center and Beckman Research Center, Duarte, California, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
authors.forename: Leroy F
authors.initials: LF
authors.lastname: Liu
authors.affiliation: Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan. PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hung-Yun
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA. Albany Medical College, Albany, New York, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Davis
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D039302:Integrin alphaVbeta3; D013267:Stilbenes; D000077185:Resveratrol