title: Male contraceptive Adjudin is a potential anti-cancer drug.
abstract: Adjudin, also known as AF-2364 and an analog of lonidamine (LND), is a male contraceptive acting through the induction of premature sperm depletion from the seminiferous epithelium when orally administered to adult rats, rabbits or dogs. It is also known that LND can target mitochondria and block energy metabolism in tumor cells. However, whether Adjudin exhibits any anti-cancer activity remains to be elucidated. Herein we described the anti-proliferative activity of Adjudin on cancer cells in vitro and on lung and prostate tumors inoculated in nude mice. We found that Adjudin induced apoptosis in cancer cells through a Caspase-3-dependent pathway. Further experiments revealed that Adjudin could trigger mitochondrial dysfunction in cancer cells, apparently affecting the mitochondrial mass, inducing the loss of mitochondrial membrane potential and reducing cellular ATP levels. Intraperitoneal administration of Adjudin to tumor-bearing athymic nude mice also significantly suppressed the lung and prostate tumor growth. When used in combination with cisplatin, Adjudin enhances the sensitivity to cisplatin-induced cancer cell cytotoxicity. Taken together, these findings have demonstrated that Adjudin may be a potential drug for cancer therapy.
authors.affiliation: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
authors.forename: Qian Reuben
authors.initials: QR
authors.lastname: Xie
authors.forename: Yewei
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Shao
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Tengyuan
authors.initials: T
authors.lastname: Liu
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.forename: Boshi
authors.initials: B
authors.lastname: Wang
authors.forename: Dolores D
authors.initials: DD
authors.lastname: Mruk
authors.forename: Bruno
authors.initials: B
authors.lastname: Silvestrini
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
authors.forename: Weiliang
authors.initials: W
authors.lastname: Xia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy*
chemical_list: C432482:1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide; D000970:Antineoplastic Agents; D003272:Contraceptive Agents, Male; D006834:Hydrazines; D007191:Indazoles; D002945:Cisplatin