کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3947526 | 1254455 | 2008 | 10 صفحه PDF | دانلود رایگان |

ObjectiveA novel indole ethyl isothiocyanate derivative (7Me-IEITC) was defined as a potent growth-suppressing agent to cell lines derived from ovarian cancers. Key mechanisms of the cellular response in vitro were studied and suggest a potential of 7Me-IEITC as a therapeutic drug.MethodsThe viability of ovarian cancer cell lines (SKOV-3, OVCAR-3) in comparison to pancreatic and prostate cancer cell lines, primary fibroblast and immortalized trophoblasts after treatment with 7Me-IEITC was analyzed. Morphological and apoptotic responses of SKOV-3 were studied by fluorescence microscopy (DAPI staining, TUNEL assay). SKOV-3 proliferation was estimated by a standardized BrdU incorporation assay. The phosphorylation of MAP-Kinases, pro-survival factors and the activation of caspases and PARP-1 were analyzed by western blotting. Changes of the mitochondrial transmembrane-potential and in cell-cycle progression were studied by FACS analysis. MAP-Kinase and caspase inhibitors were employed in cytotoxicity studies.Results7Me-IEITC selectively reduced the viability of SKOV-3, OVCAR-3, BXPC-3 and PC-3 cells (IC50 values ≤ 5 μM), while the viability of fibroblasts or trophoblasts remained un-affected at concentrations below 20 μM. 7Me-IEITC treatment down-regulated pro-survival kinases and transcription factors (STAT-3, IKKα and NF-κB), caused rapid loss of the mitochondrial transmembrane-potential and inactivation of PARP-1 along with activation of caspases. The use of p38 MAP-Kinase-and caspase inhibitors suppressed the cytotoxicity of the drug. 7Me-IEITC acted as an anti-proliferative agent and arrested the cell-cycle progression of SKOV-3 in G2/M phase.Conclusion7Me-IEITC is a potent and growth-suppressing agent to cell lines derived from ovarian cancers by causing deactivation of survival signals, apoptosis, and cell-cycle arrest.
Journal: Gynecologic Oncology - Volume 109, Issue 2, May 2008, Pages 240–249