Apogossypolone (ApoG2) induces ROS-dependent apoptosis and reduces invasiveness of PC12 cells in vitro and in vivo

作者:Lin, Dengqiang; Li, Xiaoxia; Xu, Lieyu; Lian, Jianpo; Xu, Yunze; Meng, Li; Xie, Xin; Wang, Xiaojing; He, Hongchao; Xu, Danfeng; Wang, Chenghe*; Zhu, Yu*
来源:American Journal of Translational Research, 2017, 9(9): 3990-4002.

摘要

Malignant pheochromocytoma is accurately diagnosed only at occurrence of metastatic foci. However, at that time, patients are less likely to get many benefits from traditional chemotherapy. Over-expression of BCL-2 family proteins is tightly correlated with progression of pheochromocytoma. ApoG2, as the most potent gossypol derivative, has exhibited anti-tumor activities in various tumors. In the present study, we found that the staining degree of Bcl-2 being stronger than Bax was more frequently observed in pheochromocytoma than adrenocorticohy-perplasia, which was possibly related to shorter overall survival. In addition, ApoG2 could induce apoptosis through up-regulation of Bax and down-regulation of Bcl-2, increasing reactive oxygen species (ROS) levels, inducing cytochrome C release and cleaving caspase proteins. Most importantly, those inhibition effects were blocked by caspase activation inhibitor Z-VAD-fmk and antioxidant N-acetyl-L-cysteine. The above results were further confirmed in vivo. Furthermore, ApoG2 could effectively inhibit tumor movement capabilities. Altogether, our results indicated that ApoG2 was a potential effective target drug for pheochromocytoma.