Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six new withanolides (1-6) along with eleven known ones (7-17) were isolated from the leaves of Withania aristata. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques. Semisynthesis of the minority metabolites 7 and 15 from compounds 6 and 9, respectively, as starting material, was performed. The isolated compounds as well as three derivatives (7a, 9a and 9b) of withaferin A were evaluated for cytotoxicity against HeLa (carcinoma of the cervix), A-549 (lung carcinoma) and MCF-7 (breast adenocarcinoma) human cancer cell lines, and against normal Vero cells (African green monkey kidney). Five compounds from this series (8, 9a, 9b, 11 and 13) exhibited potent antiproliferative effects on the tumor cells, even higher than the well known anticancer agent, withaferin A (9). Phosphatidylserine externalization, chromatin condensation, and caspase-3 activation clearly indicated apoptosis as a mechanism of action. The structure-activity relationship revealed valuable information on the pharmacophore for withanolide-type compounds.
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PMID:Withaferin A-related steroids from Withania aristata exhibit potent antiproliferative activity by inducing apoptosis in human tumor cells. 2270 1

Cervical carcinoma is a life-threatening illness posing considerable danger to women's health. microRNAs (miRNAs) have been shown to regulate multiple cellular events, including growth and proliferation, and miR-187 is thought to regulate the growth and apoptosis of certain cell types. Our study focused on the influence of miR-187 on the growth, proliferation, and apoptosis of SiHa cervical carcinoma cells, and explored the mechanism behind its pro-apoptotic effect. miR-187 and control (scrambled) miRNA were synthesized with a standard protocol and lipofected into SiHa cells. Thiazolyl blue tetrazolium bromide assays and tests of caspase-3 activity were then performed to examine growth, proliferation, and apoptosis by flow cytometry. Small interfering RNA (siRNA) and an expression plasmid were synthesized for inhibition and overexpression of Bcl-2, respectively, and following their transfection, western blotting was used to examine Bcl-2 protein levels. Compared to transfection with control miRNA, miR-187 significantly reduced SiHa cell growth and decreased Bcl-2 expression. Increased translocation of phosphatidylserine and activation of caspase-3 were observed in miR-187-transfected cells. Moreover, inhibition of Bcl-2 enhanced the pro-apoptotic effect of this miRNA, while Bcl-2 overexpression had the opposite effect. miR-187 inhibits the growth and proliferation of SiHa cells, and induces their apoptosis via downregulation of Bcl-2. Bcl-2 represents a potential therapeutic target for cervical carcinoma.
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PMID:miR-187 induces apoptosis of SiHa cervical carcinoma cells by downregulating Bcl-2. 2812