期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 118, 期 -, 页码 34-46出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.04.025
关键词
Oxindole; Knoevenagel condensation; Benzylideneindolin-2-one; Heterocycles; Anticancer; Apoptosis
资金
- DoP, Ministry of Chemicals AMP
- Fertilizers, Govt. of India
- SERB, DST, Govt. of India [YSS-2015-001709]
A series of new (Z)-3-(3'-methoxy-4'-(2-amino-2-oxoethoxy)benzylidene)indolin-2-one derivatives has been synthesized and evaluated for their cytotoxic activity against selected human cancer cell lines of prostate (PC-3 and DU-145), breast (BT-549 and MDA-MB-231) and non-tumorigenic prostate epithelial cells (RWPE-1). Among the tested, one of the compounds 4p exhibited potent cytotoxicity selectively on prostate cancer cell lines (PC-3 and DU-145; IC50: 1.89 +/- 0.6 and 1.94 +/- 0.2 mu M, respectively). Further experiments were conducted with 4p on PC-3 cancer cells to study the mechanisms of growth inhibition and apoptosis inducing effect. Treatment of PC-3 cells with test compound 4p resulted in inhibition of cell migration through disorganization of F-actin protein. The flow-cytometry analysis results showed that the compound arrested PC-3 cancer cells in the G2/M phase of cell cycle in a dose dependent manner. Hoechst staining and annexin-V binding assay revealed that the compound 4p inhibited tumor cell proliferation through induction of apoptosis. Western blot studies demonstrated that the compound 4p treatment led to activation of caspase-3, increased, expression of pro-apoptotic Bax and significantly decreased expression of anti-apoptotic Bcl-2 in human prostate cancer PC-3 cells. In addition, the mitochondrial membrane potential (Delta Psi m) was also affected and the levels of intracellular Ca2+ were raised. (C) 2016 Elsevier Masson SAS. All rights reserved.
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