title: Inhibition of prostate cancer growth by solanine requires the suppression of cell cycle proteins and the activation of ROS/P38 signaling pathway.
abstract: Solanine, a naturally steroidal glycoalkaloid in nightshade (Solanum nigrum Linn.), can inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism of solanine-suppressing prostate cancer cell growth remains to be elucidated. This study investigates the inhibition mechanism of solanine on cancer development in vivo and in cultured human prostate cancer cell DU145 in vitro. Results show that solanine injection significantly suppresses the tumor cell growth in xenograft athymic nude mice. Solanine regulates the protein levels of cell cycle proteins, including Cyclin D1, Cyclin E1, CDK2, CDK4, CDK6, and P21 in vivo and in vitro. Also, in cultured DU145 cell, solanine significantly inhibits cell growth. Moreover, the administration of NAC, an active oxygen scavenger, markedly reduces solanine-induced cell death. Blockade of P38 MAPK kinase cannot suppress reactive oxygen species (ROS), but can suppress solanine-induced cell apoptosis. Also, inhibition of ROS by NAC inactivates P38 pathway. Taken together, the data suggest that inhibition of prostate cancer growth by solanine may be through blocking the expression of cell cycle proteins and inducing apoptosis via ROS and activation of P38 pathway. These findings indicate an attractive therapeutic potential of solanine for suppression of prostate cancer.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Pan
authors.affiliation: Sun Yat-sen Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Urology, Gao Zhou People's Hospital, Gaozhou, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Caiyong
authors.initials: C
authors.lastname: Lai
authors.affiliation: Department of Urology, Zhuhai People's Hospital, Zhuhai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Genlong
authors.initials: G
authors.lastname: Jiao
authors.affiliation: Department of Urology, Inner Mongolia People's Hospital, Hohhot, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Qizhao
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012992:Solanine / Q000494:pharmacology*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D001688:Biological Products; D018797:Cell Cycle Proteins; D017382:Reactive Oxygen Species; D012992:Solanine; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cell cycle proteins; P38; prostate cancer; reactive oxygen species; solanine