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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 poorly 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-acetyl-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.