title: Lycorine hydrochloride selectively inhibits human ovarian cancer cell proliferation and tumor neovascularization with very low toxicity.
abstract: Uncontrolled tumor cell proliferation and robust neovascularization are prominent features of aggressive ovarian cancers. Although great efforts in anti-ovarian cancer therapy have been made in the past 4 decades, the 5-year survival rates for ovarian cancer patients are still poor, and effective drugs to cure ovarian cancer patients are absent. In this study, we evaluated the anti-cancer effects of lycorine hydrochloride (LH), a novel anti-ovarian cancer agent, using the highly-invasive ovarian cancer cell line, Hey1B, as a model. Our data showed that LH effectively inhibited mitotic proliferation of Hey1B cells (half maximal inhibitory concentration=1.2μM) with very low toxicity, resulting in cell cycle arrest at the G2/M transition through enhanced expression of the cell cycle inhibitor p21 and marked down-regulation of cyclin D3 expression. Moreover, LH suppressed both the formation of capillary-like tubes by Hey1B cells cultured in vitro and the ovarian cancer cell-dominant neovascularization in vivo when administered to Hey1B-xenotransplanted mice. LH also suppressed the expression of several key angiogenic genes, including VE-cadherin, vascular endothelial growth factor, and Sema4D, and reduced Akt phosphorylation in Hey1B cells. These results suggest that LH selectively inhibits ovarian cancer cell proliferation and neovascularization and is a potential drug candidate for anti-ovarian cancer therapy.
authors: Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Soochow University, Suzhou, Jiangsu 215006, China.
authors: Zhifei
authors: Z
authors: Cao
authors: Di
authors: D
authors: Yu
authors: Shilong
authors: S
authors: Fu
authors: Gaochuan
authors: G
authors: Zhang
authors: Yanyan
authors: Y
authors: Pan
authors: Meimei
authors: M
authors: Bao
authors: Jian
authors: J
authors: Tu
authors: Bingxue
authors: B
authors: Shang
authors: Pengda
authors: P
authors: Guo
authors: Ping
authors: P
authors: Yang
authors: Quansheng
authors: Q
authors: Zhou
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000473:pathology*; D010617:Phenanthridines / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D047151:Amaryllidaceae Alkaloids; D015703:Antigens, CD; D000970:Antineoplastic Agents; D015820:Cadherins; D056743:Cyclin D3; D010617:Phenanthridines; D051057:Proto-Oncogene Proteins c-akt; D039961:Semaphorins; D000099152:Cadherin 5; C534696:CCND3 protein, human; C093224:CD100 antigen; C015330:lycorine