title: A novel metformin derivative, HL010183, inhibits proliferation and invasion of triple-negative breast cancer cells.
abstract: Mounting evidence suggests that metformin (N,N-dimethylbiguanide), a widely prescribed drug for the treatment of type II diabetes, exerts an anti-tumor effect on several cancers including breast cancer. Breast cancer has been estimated as one of the most commonly diagnosed types of cancer among women. In particular, triple-negative breast cancers are associated with poor prognosis and metastatic growth. In the present study, we synthesized a novel metformin derivative 5 (HL010183) and metformin salts, 9a, 9b, and 9c (metformin gamma-aminobutyric acid (GABA) salt, metformin pregabalin salt and metformin gabapentin salt), which exerted more potent inhibitory effects on the proliferation and invasiveness of Hs578T triple-negative breast carcinoma cells than metformin. Importantly, 5 showed approximately 100-fold more potent effects compared to metformin. In a triple-negative breast cancer xenograft model, 5 showed a comparable degree of inhibitory effect on in vivo tumor growth at the 100mg/kg dose to that of metformin at 500 mg/kg. Our results clearly demonstrate that 5 exerts a potent anti-tumor effect both in vitro and in vivo, paving the way for a strategy for treatment of triple-negative breast cancer.
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 132-714, Republic of Korea.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Koh
authors.affiliation: Energy Materials Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Jong-Cheol
authors.initials: JC
authors.lastname: Lee
authors.affiliation: HanAll Biopharma Co., Ltd, Central Research Institute, Daejeon, Republic of Korea.
authors.forename: Changhee
authors.initials: C
authors.lastname: Min
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 132-714, Republic of Korea. Electronic address: armoon@duksung.ac.kr.
authors.forename: Aree
authors.initials: A
authors.lastname: Moon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008687:Metformin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008687:Metformin