Biomol Ther  
Treatment with Phytoestrogens Reversed Triclosan and Bisphenol A-Induced Anti-Apoptosis in Breast Cancer Cells
Geum-A Lee, Kyung-Chul Choi* and Kyung-A Hwang*
Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea
E-mail: kchoi@cbu.ac.kr (Choi KC), hka9400@naver.com (Hwang KA)
Tel: +82-43-261-3664 (Choi KC), +82-43-249-1745 (Hwang KA)
Fax: +82-43-267-3150 (Choi KC), +82-43-267-3150 (Hwang KA)
Received: August 14, 2017; Revised: September 22, 2017; Accepted: October 23, 2017; Published online: January 9, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Triclosan (TCS) and bisphenol A (BPA) are endocrine-disrupting chemicals that interfere with the hormone or endocrine system and may cause cancer. Kaempferol (Kaem) and 3,3′-diindolylmethane (DIM) are phytoestrogens that play chemopreventive roles in the inhibition of carcinogenesis and cancer progression. In this study, the influence of TCS, BPA, Kaem, and DIM on proliferation and apoptotic abilities of VM7Luc4E2 breast cancer cells were examined. MTT assay revealed that TCS (0.1–10 μM), BPA (0.1–10 μM) and E2 (0.01–0.0001 μM) induced significant cell proliferation of VM7Luc4E2 cells, which was restored to the control (0.1% DMSO) by co-treatment with Kaem (30 μM) or DIM (15 μM). Reactive oxygen species (ROS) production assays showed that TCS and BPA inhibited ROS production of VM7Luc4E2 cells similar to E2, but that co-treatment with Kaem or DIM on VM-7Luc4E2 cells induced increased ROS production. Based on these results, the effects of TCS, BPA, Kaem, and DIM on protein expression of apoptosis and ROS production-related markers such as Bax and Bcl-xl, as well as endoplasmic reticulum (ER) stress-related markers such as eIF2α and CHOP were investigated by Western blot assay. The results revealed that TCS, and BPA induced anti-apoptosis by reducing ROS production and ER stress. However, Kaem and DIM effectively inhibited TCS and BPA-induced anti-apoptotic processes in VM7Luc4E2 cells. Overall, TCS and BPA were revealed to be distinct xenoestrogens that enhanced proliferation and anti-apoptosis, while Kaem and DIM were identified as natural chemopreventive compounds that effectively inhibited breast cancer cell proliferation and increased anti-apoptosis induced by TCS and BPA.
Keywords: Kaempferol, 3,3′-diindolylmethane, Triclosan, Bisphenol A, Apoptosis, Reactive oxygen species


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