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Cellular Mechanisms of a New Pyrazinone Compound that Induces Apoptosis in SKOV-3 Cells

  • Wang, Guan (Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University) ;
  • Jiang, Meng-Ying (Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University) ;
  • Meng, Ying (Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University) ;
  • Song, Hong-Rui (Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University) ;
  • Shi, Wei (Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University)
  • Published : 2014.01.30

Abstract

We screened a small molecular library that was designed and independently synthesized in vitro and found a new drug (MY-03-01) that is active against ovarian cancer. We established that MY-03-01 effectively inhibited SKOV-3 cell survival in a dose-dependent manner, based on cell viability rates, and that it not only induced SKOV-3 apoptosis by itself, but also did so synergistically with paclitaxel. Secondly, when MY-03-01 was applied at $40{\mu}M$, its hemolytic activity was less than 10%, compared with the control, and there was almost no damage to nor mal cells at this concentration. In addition, we used DAPI staining and flow cytometry to show that MY-03-01 could significantly induce apoptosis of SKOV-3 cells. Finally, we found that MY-03-01 likely induced SKOV-3 apoptosis by activating caspase3 and caspase9 through the mitochondrial pathway.

Keywords

References

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