S-Space College of Medicine/School of Medicine (의과대학/대학원) Program in Cancer Biology (협동과정-종양생물학전공) Theses (Master's Degree_협동과정-종양생물학전공)
Reactive oxygen species (ROS)-mediated Akt inhibition by genistein induces autophagic cell death in ovarian cancer cells
난소암 세포주에서 Genistein에 의해 유도되는 활성산소에 의한 Akt 저해와 자가포식의 항암작용과 기전 연구
- 의과대학 협동과정 종양생물학전공
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 협동과정 종양생물학전공, 2014. 2. 송용상.
- Cancer cells are vulnerable to reactive oxygen species (ROS) due to redox imbalance. Recently, genistein, a polyphenolic compound, has shown to have pro-oxidant activity, causing cell death in several types of malignancies, including breast, prostate and hematologic cancers. Here, we show that in ovarian cancer cells genistein invokes the cell death through autophagy and the generation of ROS. As a matter of fact, genistein increases the level of ROS giving rise to apoptosis and autophagy. In addition, pretreatment with the autophagy inhibitor, 3-methyladenine (3-MA), suppressed genistein-mediated cell death in ovarian cancer cells. These results suggest that autophagy is involved in genistein-mediated cell death. Interestingly, genistein-mediated cell death was restored by ROS scavengers, such as N-acetyl-L-cysteine (NAC) and Trolox, suggesting an essential role of intrinsic ROS in genistein-induced autophagic cell death. Moreover, genistein stimulates the inhibition of the AKT/mTOR signaling pathway through a ROS-mediated mechanism. Taken together, our study suggests that genistein-mediated cell death through inhibition of the AKT/mTOR signaling pathway and ROS-induced autophagy is important for cancer cell killing.