癌症2011，Vol.30Issue(1)：41-53,13.
Apogossypolone targets mitochondria and light enhances its anticancer activity by stimulating generation of singlet oxygen and reactive oxygen species
Apogossypolone targets mitochondria and light enhances its anticancer activity by stimulating generation of singlet oxygen and reactive oxygen species
Zhe-Yu Hu 1Jing Wang 2Gang Cheng 3Xiao-Feng Zhu 1Peng Huang 2Dajun Yang 4Yi-Xin Zeng1
作者信息
- 1. State Key Laboratory of Oncology in South China,Guangzhou,Guangdong 510060,P.R.China
- 2. Department of Experimental Research,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong 510060,P.R.China
- 3. The First Hospital of Changsha City,Changsha,Hunan 410005,P.R.China
- 4. Departrnent of Molecular Pathology,The University of Texas MD Anderson Cancer Center,Houston,Texas 77030,USA
- 折叠
摘要
Abstract
Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the pooriy differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyI-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, APOG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC.关键词
Apogossypolone/ mitochondria/ singlet oxygen/ reactive oxygen species/ photodynamic therapyKey words
Apogossypolone/ mitochondria/ singlet oxygen/ reactive oxygen species/ photodynamic therapy引用本文复制引用
Zhe-Yu Hu,Jing Wang,Gang Cheng,Xiao-Feng Zhu,Peng Huang,Dajun Yang,Yi-Xin Zeng..Apogossypolone targets mitochondria and light enhances its anticancer activity by stimulating generation of singlet oxygen and reactive oxygen species [J].癌症,2011,30(1):41-53,13.
