Biomol Ther  
MS-5, a Naphthalene Derivative, Induces the Apoptosis of an Ovarian Cancer Cell Caov-3 by Interfering with the Reactive Oxygen Species Generation
Eunsook Ma1,†, Seon-Ju Jeong1,†, Joon-Seok Choi1, Thi Ha Nguyen1, Chul-Ho Jeong2,* and Sang Hoon Joo1,*
1Department of Pharmacy, Daegu Catholic University, Gyeongsan 38430,
2College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea
E-mail: chjeong75@kmu.ac.kr (Jeong CH), sjoo@cu.ac.kr (Joo SH)
Tel: +82-53-580-6638 (Jeong CH), +82-53-850-3614 (Joo SH)
Fax: +82-53-580-5164 (Jeong CH), +82-53-359-6729 (Joo SH)
The first two authors contributed equally to this work.
Received: January 24, 2018; Revised: February 6, 2018; Accepted: February 12, 2018; Published online: April 2, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Reactive oxygen species (ROS) are widely generated in biological processes such as normal metabolism and response to xenobiotic exposure. While ROS can be beneficial or harmful to cells and tissues, generation of ROS by diverse anti-cancer drugs or phytochemicals plays an important role in the induction of apoptosis. We recently identified a derivative of naphthalene, MS-5, that induces apoptosis of an ovarian cell, CAOV-3. Interestingly, MS-5 induced apoptosis by down-regulating the ROS. Cell viability was evaluated by water-soluble tetrazolium salt (WST-1) assay. Apoptosis was evaluated by flow cytometry analysis. Intracellular ROS (H2O2), mitochondrial superoxide, mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was assessed by western blotting. The level of ATP was measured using ATP Colorimetric/Fluorometric Assay kit. MS-5 inhibited growth of ovarian cancer cell lines, CAOV-3, in a concentration- and time-dependent manner. MS-5 also induced G1 cell cycle arrest in CAOV-3 cells, while MS-5 decreased intracellular ROS generation. In addition, cells treated with MS-5 showed the decrease in MMP and ATP production. In this study, we found that treatment with MS-5 in CAOV-3 cells induced apoptosis but decreased ROS level. We suspect that MS-5 might interfere with the minimum requirements of ROS for survival. These perturbations appear to be concentration-dependent, suggesting that MS-5 may induce apoptosis by interfering with ROS generation. We propose that MS-5 may be a potent therapeutic agent for inducing apoptosis in ovarian cancer cell through regulation of ROS.
Keywords: Reactive oxygen species, Apoptosis, Anti-cancer effect


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