title: Anti-angiogenic effects of trabectedin (Yondelis; ET-743) on human breast cancer cells.
abstract: Trabectedin, a tetrahydroisoquinoline alkaloid derived from a Caribbean tunicate Ecteinascidia turbinata, has been shown to have antitumor effects. In this study, we assessed the possible anti-angiogenic effects of trabectedin on human umbilical vein endothelial cells (HUVECs) and breast cancer cell lines. An XTT cell viability assay was used to determine cytotoxicity. A scratch assay was used to detect the migration of cells after trabectedin treatment. Angiogenic cytokine profiles of breast cancer cell lines, before and after treatment with trabectedin, were investigated using an angiogenesis antibody array. Changes in mRNA expression levels of VEGF were evaluated using qRT-PCR. Trabectedin inhibited the viability of HUVECs and breast cancer cells in a concentration- and time-dependent manner. The migration of both HUVECs and breast cancer cells was suppressed by trabectedin treatment. Angiogenic cytokines which are known to regulate tumorigenicity and angiogenesis, such as GM-CSF, IGFBP-2, VEGF, and uPA, were inhibited, while several anti-angiogenic cytokines such as TIMP-1 and Serpin E1were induced in breast cancer cells. Furthermore, expression levels of VEGF mRNA were inhibited in all breast cancer cells tested. Although additional studies are needed to elucidate the molecular mechanisms underlying the anti-angiogenic activity of trabectedin, our results suggest that trabectedin may act as a potential anti-angiogenic agent in breast cancer cells.
authors.affiliation: Section of Molecular Biology, Department of Biology, Faculty of Science and Letters, Celal Bayar University, 45140, Muradiye, Manisa, Turkey.
authors.forename: Harika
authors.initials: H
authors.lastname: Atmaca
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Celal Bayar University, 45030, Manisa, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Uzunoglu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004149:Dioxoles / Q000494:pharmacology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis; D061986:MCF-7 Cells; D009389:Neovascularization, Pathologic; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D000077606:Trabectedin; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D018971:Insulin-Like Growth Factor Binding Protein 2; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C560822:TIMP1 protein, human; D044005:Tetrahydroisoquinolines; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000077606:Trabectedin
keywords: ET-743); HUVECs; VEGF; angiogenic cytokines; breast cancer cells; trabectedin (Yondelis