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

We evaluated molecular events associated with apoptosis induced by Epothilone B (EpoB, Patupilone) and paclitaxel (PTX) in human ovarian papillary serous adenocarcinoma cell line (OV-90). Epothilones are compounds of natural origin with mechanisms of action similar to taxanes, but with more potent antiproliferative activity. Apoptosis was one of the major forms of cell death induced by EpoB. The mode of cell death was assessed colorimetrically, fluorimetrically, cytometry, and by immunoblot analyses through measuring DNA fragmentation, the level of TRAIL, the cleavage of poly(ADP-ribose) polymerase (PARP) and the activation of caspase-9, -8 and -3. We measured also additional markers of apoptosis, like phosphatidylserine externalization and morphological changes. Moreover, we estimated glycoprotein P (P-gp) activity in OV-90 ovarian cancer cell line. The studies indicated that the extrinsic pathway of apoptosis, which is triggered by certain TNF family members and engages their respective receptors on the surface of the target cell, was predominant. We were the first to have demonstrated (using immunoassay) the release of TNF-related apoptosis-inducing ligand (TRAIL) after treatment with EpoB. EpoB and PTX mediate activation of both initiator caspases-8 and -9, leading to the appearance of caspase-3. In EpoB treated cells, DNA fragmentation was also detected. EpoB leads to the reduction in DNA repair capacity. In summary, we report that Epothilone B induces apoptosis in OV-90 cells via a TRAIL and caspase 8-dependent pathway. PTX leads to smaller apoptotic events in comparison to EpoB.
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PMID:Epothilone B induces human ovarian cancer OV-90 cell apoptosis via external pathway. 2572 85

Epothilones constitute a new class of microtubule-stabilizing anti-cancer agents with promising preclinical and clinical activity. However, its systemic application still causes some toxic side effects. To reduce these undesired effects, advanced drug delivery systems based on cell targeting carriers are needed currently. In this study, the high quality bacterial ghosts of the probiotic Escherichia coli Nissle 1917 (EcN) were prepared in a large scale and retained fully intact surface structures for specific attachment to mammalian cells. The EcN ghosts could be efficiently loaded with the low hydrophilic drug Epothilone B (Epo B) and the maximal load efficiency was approximately 2.5% (w/w). Cytotoxicity assays revealed that Epo B-ghosts exhibited enhanced anti-proliferative properties on the HeLa cells. The Epo B associated with EcN ghosts was more cytotoxic at least 10 times than the free Epo B at the same concentrations. Apoptosis assays showed that both Epo B-ghosts and free Epo B induced time course-dependent apoptosis and necrosis in HeLa cells, respectively. While the former induced more apoptosis and necrosis than the latter. Furthermore, the cytochrome C release and the activation of caspase-3 were more remarkable after treatment with the Epo B-ghosts compared to the free Epo B, which implied that Epo B-ghosts might more effectively induce the apoptosis mediated by mitochondrial pathway in HeLa cells. Therefore, the higher anti-proliferative effects of the Epo B-ghosts on the HeLa cells were mediated by mitochondrial pathway of apoptosis. The EcN ghosts may provide a useful drug delivery carrier for drug candidates in cancer therapy.
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PMID:Enhanced anti-proliferative efficacy of epothilone B loaded with Escherichia coli Nissle 1917 bacterial ghosts on the HeLa cells by mitochondrial pathway of apoptosis. 2991 54