title: Jatrorrhizine hydrochloride inhibits the proliferation and neovascularization of C8161 metastatic melanoma cells.
abstract: Malignant melanoma is the most aggressive form of skin cancer. Although various antimelanoma approaches have been used in the clinics to treat the disease over the last three decades, none of the drugs significantly prolonged the survival of metastatic melanoma patients; hence, effective drugs against metastatic melanoma are highly desired. In this study, we explored an antimetastatic melanoma agent derived from traditional Chinese medicinal herbs and found that jatrorrhizine hydrochloride (JH), an active component of the traditional Chinese medicinal herb Coptis chinensis, inhibited the proliferation and neovascularization of C8161 human metastatic melanoma cells. JH suppressed C8161 cell proliferation in a dose-dependent manner, with a half-maximal inhibitory concentration of 47.4±1.6 μmol/l; however, it did not induce significant cellular apoptosis at doses up to 320 μmol/l. Mechanistic studies showed that JH-induced C8161 cell cycle arrest at the G0/G1 transition, which was accompanied by overexpression of the cell cycle-suppressive genes p21 and p27 at higher doses. Moreover, JH reduced C8161 cell-mediated neovascularization in vitro and in vivo and impeded the expression of the gene for VE-cadherin, a key protein in tumor vasculogenic mimicry and angiogenesis. Taken together, the effective inhibitory effects of JH on metastatic melanoma cell proliferation and neovascularization with low toxicity suggest that JH is a potential new antimelanoma drug candidate.
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Ministry of Health, Soochow University, Jiangsu, China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Liu
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Cao
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Pan
authors.forename: Gaochuan
authors.initials: G
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Pengda
authors.initials: P
authors.lastname: Guo
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006131:Growth Inhibitors / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D006131:Growth Inhibitors; C055785:jatrorrhizine; D001599:Berberine