Journal Browser Advanced Search Help
Journal Browser Advanced search HELP
J Breast Cancer. 2016 Jun;19(2):122-132. English. Original Article.
Narayanan PD , Nandabalan SK , Baddireddi LS .
Department of Biotechnology, Anna University, Chennai, India.
Department of Biochemistry, University of Madras, Chennai, India.
Centre for Food Technology, Department of Biotechnology, Anna University, Chennai, India.

PURPOSE: In this study, we investigated the molecular mechanism involved in ethanol (EtOH)-mediated proliferation of breast cancer cells. METHODS: EtOH concentration was optimized by studying its effect on cell proliferation in MCF-7 and MDA MB-231 cells. We used flow cytometry and immunoblot analysis to evaluate the increased proliferation caused by the optimized concentrations of EtOH. The mechanism of EtOH-mediated proliferation was determined using reactive oxygen species (ROS) release assay, reverse transcription polymerase chain reaction, and immunoblot studies. Gene silencing followed by quantitative real-time polymerase chain reaction studies and inhibitor studies indicated the involvement of signal transducer and activator of transcription 3 (STAT3) in EtOH-mediated breast cancer proliferation. RESULTS: Exposure to EtOH caused an increase in cell proliferation and an accumulation of cells in S-phase in MCF-7 (347 µM EtOH) and MDA MB-231 (173 µM EtOH) cells. Additionally, increased release of ROS and the expression of pro-inflammatory cytokines, such as interleukin 6 and tumor necrosis factor α, confirmed that the proliferation was induced by the ROS-linked inflammatory response in breast cancer. The proinflammatory response was followed by phosphorylation of STAT3. The importance of STAT3 activation in EtOH-mediated proliferation was confirmed through the silencing of STAT3, followed by an investigation on the expression of cyclins and matrix metalloproteinases. Finally, studies using specific inhibitors indicated that the EtOH-mediated effect on STAT3 activation could be regulated by phosphoinositide-3-kinase and Janus kinase 2. CONCLUSION: The study demonstrates the involvement of STAT3 signaling in EtOH-mediated breast cancer proliferation.

Copyright © 2019. Korean Association of Medical Journal Editors.