activation of amp-activated protein kinase by 3,3′-diindolylmethane (dim) is associated with human prostate cancer cell death in vitro and in vivo活化蛋白激酶的激活3,3u2032-diindolylmethane(暗)与人类前列腺癌的细胞死亡在体外和体内.pdfVIP

Activation of AMP-Activated Protein Kinase by 3,39- Diindolylmethane (DIM) Is Associated with Human Prostate Cancer Cell Death In Vitro and In Vivo 1 2 1 2 1,2 1,2 Di Chen , Sanjeev Banerjee , Qiuzhi C. Cui , Dejuan Kong , Fazlul H. Sarkar *, Q. Ping Dou * 1 Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, Michigan, United States of America, 2 Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, Michigan, United States of America Abstract There is a large body of scientific evidence suggesting that 3,3 9-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. However, the precise molecular mechanism(s) for the anti-cancer effects of B-DIM have not been fully elucidated. In the present study, we investigated whether AMP-activated protein kinase (AMPK) is a molecular target of B-DIM in human prostate cancer cells. Our results showed, for the first time, that B-DIM could activate the AMPK signaling pathway, associated with suppression of the mam