S-Space College of Agriculture and Life Sciences (농업생명과학대학) Dept. of Agricultural Biotechnology (농생명공학부) Theses (Master's Degree_농생명공학부)
ROS accumulation by PEITC selectively kills ovarian cancer cells via UPR-mediated apoptosis
PEITC에 의해 축적된 활성산소로 인한 난소암세포주의 UPR 매개 사멸기전 연구
- 농업생명과학대학 농생명공학부
- Issue Date
- 서울대학교 대학원
- Unfolded Protein Response; β-phenethyl isothiocyanate; ovarian cancer; Reactive Oxygen Species; Apoptosis
- 학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부(바이오모듈레이션전공), 2015. 6. 송용상.
- Unfolded protein response (UPR) is crucial for both survival and death of mammalian cells, which is regulated by reactive oxygen species (ROS) and nutrient depletion. In this study, we demonstrated the effect of ROS-accumulation, induced by β-phenethyl isothiocyanate (PEITC), on UPR mediated apoptosis in ovarian cancer cells. We used ovarian cancer cell lines, PA-1 and SKOV-3, with different p53 status (wild- and null- type, respectively). PEITC caused increased ROS-accumulation and inhibited proliferation selectively in ovarian cancer cells, and glutathione (GSH) depletion in SKOV-3. However, PEITC did not cause any effect in normal ovarian epithelial cells and peripheral blood mononuclear cells. After 48 h of PEITC treatment (5 µM), apoptotic cell death was shown to increase significantly in the ovarian cancer cells and not in the normal cells. The key regulator of UPR-mediated apoptosis, CHOP/GADD153 and ER resident chaperone BiP/GRP78 were parallely up-regulated with activation of two major sensors of the UPR (PERK and ATF-6 in PA-1
PERK, and IRE1α in SKOV-3) in response to ROS accumulation induced by PEITC (5 µM). ROS scavenger, N-acetyl-L-cysteine (NAC), attenuated the effect of PEITC on UPR signatures (P-PERK, IRE1α, CHOP/GADD153, and BiP/GRP78), suggesting the involvement of ROS in UPR-mediated apoptosis. Altogether, PEITC induces UPR-mediated apoptosis in ovarian cancer cells via accumulation of ROS in a cancer-specific manner.