Biomol Ther.  2019 Jan;27(1):48-53. 10.4062/biomolther.2018.020.

MS-5, a Naphthalene Derivative, Induces the Apoptosis of an Ovarian Cancer Cell CAOV-3 by Interfering with the Reactive Oxygen Species Generation

• Ma E
• Jeong SJ
• Choi JS
• Nguyen TH
• Jeong CH
• Joo SH

• KMID: 2432066
• DOI: http://doi.org/10.4062/biomolther.2018.020

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 (Hâ‚‚Oâ‚‚), 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.

Keyword

Reactive oxygen species; Apoptosis; Anti-cancer effect

MeSH Terms

Adenosine Triphosphate
Apoptosis*
Biological Processes
Blotting, Western
Cell Line
Cell Survival
Flow Cytometry
G1 Phase Cell Cycle Checkpoints
Membrane Potential, Mitochondrial
Metabolism
Ovarian Neoplasms*
Phytochemicals
Reactive Oxygen Species*
Superoxides
Adenosine Triphosphate
Reactive Oxygen Species
Superoxides