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

The aim of this study was to investigate the effects of acriflavine on viability and induction of apoptosis and autophagy in human osteosarcoma cell lines MG63. Inhibition of cell proliferation by acriflavine was determined using MTT assay. Induction of apoptosis was examined by measuring the changes in expression of Bcl-2 and Bax in messenger RNA (mRNA) and protein levels. Identification of the proteolytic cleavage of poly (ADP)-ribose polymerase (PARP) and caspase-3 and caspase-9 was carried out to study apoptotic cell death. Autophagic effects were examined by quantitation of mRNA expression of autophagy protein 5 (Atg5) and Beclin1 and identifying accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II. The results showed acriflavine inhibited cell proliferation of osteosarcoma cells in dose-dependent fashion. Acriflavine-induced cell death was attributed to both apoptosis and autophagy. Moreover, it was associated with changes in the levels of Bcl-2 and Bax in the osteosarcoma cells. The antiseptic agent, acriflavine, has anticancer potential through synergistic activity of apoptosis and autophagy.
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PMID:Acriflavine suppresses the growth of human osteosarcoma cells through apoptosis and autophagy. 2496 47

There is a lack of well-characterized models for pancreatic ductal adenocarcinoma (PDAC). PDAC itself is unique because of its pronounced tumor microenvironment that influences tumor progression, behavior and therapeutic resistance. Here we investigated, in patient-derived tumor xenograft (PDTX) models developed from fine needle biopsies, the cancer cells behavior, Epithelial-to-Mesenchymal Transition (EMT) and drug response. For this, we studied two behaviorally distinct PDTX models. Tumor volume measurement, histology, immuno-histochemical staining, RT-qPCR, RNA sequencing and Western blotting were used to further characterize these models and investigate the effect of two classes of drugs (gemcitabine and acriflavine (HIF-inhibitor)). The models recapitulated the corresponding primary tumors. The growth-rate of the poorly differentiated tumor (PAC010) was faster than that of the moderately differentiated tumor (PAC006) (P<0.05). The PAC010 model showed increased cell proliferation (Ki-67 staining) and markers indicating survival (increased p-AKT, p-ERK and p-NF-kB65 and suppression of cleaved PARP). Gene and protein analysis showed higher expression of mesenchymal markers in PAC010 model (e.g. VIM, SNAI2). Pathway analysis demonstrated activation of processes related to EMT, tumor progression and aggressiveness in PAC010. Gemcitabine treatment resulted in shrinking of the tumor volume and reduced proliferation in both models. Importantly, gemcitabine treatment significantly enhanced the expression of mesenchymal marker supportive of metastatic behavior and of survival pathways, particularly in the non-aggressive PAC006 model. Acriflavine had little effect on tumor growth in both models. In conclusion, we observed in this unique model of PDAC, a clear link between EMT and poor tumor differentiation and found that gemcitabine can increase EMT.
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PMID:Gemcitabine induces Epithelial-to-Mesenchymal Transition in patient-derived pancreatic ductal adenocarcinoma xenografts. 3089 78