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)

Recently, ambient air particulate matter (PM) has been shown to increase the risk of oral cancer. The most common malignant tumor in the oral cavity is oral squamous cell carcinoma (OSCC). Recent studies have revealed that surfactin, a cyclic lipopeptide generated by Bacillus subtilis, has anti-inflammatory and anti-cancer properties. However, the exact anti-cancer effects of surfactin on human OSCC and underlying molecular mechanisms remain largely unknown. In the present study, we found that treatment of SCC4 and SCC25 cells (human OSCC cell lines) with surfactin reduced the viability of SCC4 and SCC25 cells by induction of apoptosis. Surfactin-induced apoptosis was associated with caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage and was regulated by the mitochondrial pathway, exemplified by mitochondrial depolarization, mitochondrial-derived reactive oxidative species (ROS) production, cytochrome c release, up-regulation of Bad and Bax, and down-regulation of Bcl-2. Surfactin induced NADPH oxidase-dependent ROS generation, which appeared essential for the activation of the mitochondrial pathway. Surfactin-induced mitochondrial-derived ROS generation was associated with JNK1/2 activation. After treatment with surfactin, ROS caused JNK1/2-dependent cell death of SCC4 and SCC25 cells. Taken together, our findings suggest that surfactin induces mitochondria associated apoptosis of human OSCC cell lines, and surfactin may be a potential chemotherapeutic agent for future OSCC treatment.
 ...
PMID:Surfactin from Bacillus subtilis induces apoptosis in human oral squamous cell carcinoma through ROS-regulated mitochondrial pathway. 3319 89

Efficacy and mechanism of action of marine alkaloid 3,10-dibromofascaplysin (DBF) were investigated in human prostate cancer (PCa) cells harboring different levels of drug resistance. Anticancer activity was observed across all cell lines examined without signs of cross-resistance to androgen receptor targeting agents (ARTA) or taxane based chemotherapy. Kinome analysis followed by functional investigation identified JNK1/2 to be one of the molecular targets of DBF in 22Rv1 cells. In contrast, no activation of p38 and ERK1/2 MAPKs was observed. Inhibition of the drug-induced JNK1/2 activation or of the basal p38 activity resulted in increased cytotoxicity of DBF, whereas an active ERK1/2 was identified to be important for anticancer activity of the alkaloid. Synergistic effects of DBF were observed in combination with PARP-inhibitor olaparib most likely due to the induction of ROS production by the marine alkaloid. In addition, DBF intensified effects of platinum-based drugs cisplatin and carboplatin, and taxane derivatives docetaxel and cabazitaxel. Finally, DBF inhibited AR-signaling and resensitized AR-V7-positive 22Rv1 prostate cancer cells to enzalutamide, presumably due to AR-V7 down-regulation. These findings propose DBF to be a promising novel drug candidate for the treatment of human PCa regardless of resistance to standard therapy.
 ...
PMID:Efficacy and Mechanism of Action of Marine Alkaloid 3,10-Dibromofascaplysin in Drug-Resistant Prostate Cancer Cells. 3327 56


<< Previous 1 2 3 4 5 6 7