Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dried fruits of Evodia rutaecarpa Bentham have been used widely as a herbal medicine for the treatment of inflammatory disorders and abdominal pain. Benign prostatic hyperplasia (BPH) is a nonmalignant disease characterized by overgrowth of prostates. Despite the pharmacological efficacy of the fruits of E. rutaecarpa against various diseases, their effects against BPH have not been reported. Here, we investigated the inhibitory activity of a 70% ethanol extract of E. rutaecarpa (EEER) against BPH, and its underlying mechanisms regarding cell growth of BPH using BPH-1 cells. An in vitro 5α-reductase activity assay showed that EEER exhibited inhibitory activity against 5α-reductase. In BPH-1 cells, EEER treatment inhibited cell viability and reduced the expression of the proliferating cell nuclear antigen proliferating cell nuclear antigen (PCNA), cyclin D1, and phosphor-ERK1/2 proteins. Moreover, EEER also induced apoptosis, with chromatin condensation, apoptotic bodies, and internucleosomal DNA fragmentation. Regarding its underlying mechanisms, EEER exacerbated the activation of caspase-8 and caspase-3 in a concentration-dependent manner and eventually caused the cleavage of PARP. Taken together, these data demonstrated that EEER had a potent 5α-reductase inhibitory activity and that EEER treatment in BPH-1 cells inhibited cell viability via caspase-8- and caspase-3-dependent apoptosis. Therefore, EEER may be a potential phytotherapeutic agent for the treatment of BPH.
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PMID:Ethanol Extract of Evodia rutaecarpa Attenuates Cell Growth through Caspase-Dependent Apoptosis in Benign Prostatic Hyperplasia-1 Cells. 3086 29

Novel therapeutic strategies are still urgently expected for leukemia despite undisputed success of various targeted therapeutics. The antileukemia activity of Atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on human leukemia cells was investigated. Atorvastatin inhibited K562 and HL60 cell proliferation, induced G2/M cell cycle arrest in K562 cells by down-regulating cyclinB1 and cdc2, but G0/G1 arrest in HL60 cells by up-regulating p27 and down-regulating cyclinD1 and p-pRb. Atorvastatin also induced apoptosis in both cell lines, in which the reactive oxygen species (ROS)-related mitochondrial apoptotic signaling might be involved, with increase of ROS and Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (MMP), release of cytochrome C into cytosol, and activation of Bax/Caspase-9/Caspase-3/PARP pathway. Inhibition of YAP nuclear localization and activation by Atorvastatin was reversed by the addition of mevalonate, GGPP, or FPP. Further, the effects on cell cycle arrest- and apoptosis- related proteins by Atorvastatin were alleviated by addition of mevalonate, suggesting the antileukemia effect of Atorvastatin might be through mevalonate-YAP axis in K562 and HL60 cells. Our results suggest that Atorvastatin might be used for leukemia therapy while evidence of clinical efficacy is required.
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PMID:Atorvastatin Exerts Antileukemia Activity via Inhibiting Mevalonate-YAP Axis in K562 and HL60 Cells. 3164 88

Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to overcome tyrosine kinase inhibitor (TKI) resistance in epithelial growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) cells in vivo and in vitro. However, little is known about the putative induction of non-apoptotic cell death pathways by statins. We investigated the effects of pitavastatin and fluvastatin alone or in combination with erlotinib in three NSCLC cell lines and examined the activation of different cell death pathways. We assessed apoptosis via fluorometric caspase assay and poly (ADP-ribose) polymerase 1 (PARP) cleavage. Furthermore, annexinV/propidium iodide (PI) flow cytometry was performed. Small molecule inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD), necrostatin 1 (Nec1), ferrostatin 1 (Fer1), Ac-Lys-Lys-Norleucinal (Calp1) were used to characterise cell death pathway(s) putatively (co-)activated by pitavastatin/erlotinib co-treatment. Synergism was calculated by additivity and isobolographic analyses. Pitavastatin and fluvastatin induced cell death in EGFR TKI resistant NSCLC cells lines A549, Calu6 and H1993 as shown by caspase 3 activation and PARP cleavage. Co-treatment of cells with pitavastatin and the EGFR TKI erlotinib resulted in synergistically enhanced cytotoxicity compared to pitavastatin monotherapy. Flow cytometry indicated the induction of alternative regulated cell death pathways. However, only co-treatment with mevalonic acid (Mev) or the pan-caspase inhibitor zVAD could restore cell viability. The results show that cytotoxicity mediated by statin/erlotinib co-treatment is synergistic and can overcome erlotinib resistance in K-ras mutated NSCLC and relies only on apoptosis.
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PMID:Delineation of cell death mechanisms induced by synergistic effects of statins and erlotinib in non-small cell lung cancer cell (NSCLC) lines. 3196


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