PKCδ and PKCθ are PKC isoforms that activated by diacylglycerol may be inhibited calphostin C, Gö 6983 chelerythrine.

A putative anticancer plant alkaloid, Chelerythrine binds to G-quadruplexes at promoters of VEGFA, BCL2 and KRAS genes and down regulates their expression. The association of Chelerythrine to G-quadruplex at the promoters of these oncogenes were monitored using UV absorption spectroscopy, fluorescence anisotropy, circular dichroism spectroscopy, CD melting, isothermal titration calorimetry, mol...

The identification of small molecule inhibitors of antiapoptotic Bcl-2 family members has opened up new therapeutic opportunities, while the vast diversity of chemical structures and biological activities of natural products are yet to be systematically exploited. Here we report the identification of chelerythrine as an inhibitor of BclXL-Bak Bcl-2 homology 3 (BH3) domain binding through a high...

Although murine embryonic fibroblasts (MEFs) with Bax or Bak deleted displayed no defect in apoptosis signaling, MEFs with Bax and Bak double knock-out (DKO) showed dramatic resistance to diverse apoptotic stimuli, suggesting that Bax and Bak are redundant but essential regulators for apoptosis signaling. Chelerythrine has recently been identified as a Bcl-xL inhibitor that is capable of trigge...

Although clonogenic or divisional death is the main mechanism by which DNA-damaging agents demonstrate antitumor activity, recent data indicate that strategies specifically designed to trigger apoptosis may also prove to be useful antitumor agents. Protein kinase C (PKC) isoenzymes are involved in the regulation of cell proliferation, differentiation, and survival. Whereas pharmacological inhib...

A study on binding of antitumor chelerythrine to human telomeric DNA/RNA G-quadruplexes was performed by using DNA polymerase stop assay, UV-melting, ESI-TOF-MS, UV-Vis absorption spectrophotometry and fluorescent triazole orange displacement assay. Chelerythrine selectively binds to and stabilizes the K(+)-form hybrid-type human telomeric DNA G-quadruplex of biological significance, compared w...

PURPOSE Chelerythrine, a widely used broad-range protein kinase C inhibitor, induces apoptosis in many cell types. In this study, the mechanism of chelerythrine-induced apoptosis in osteosarcoma was investigated. EXPERIMENTAL DESIGN Signaling pathways activated by chelerythrine in osteosarcoma were detected by Western blots. Impacts of RAF/mitogen-activated protein kinase (MAPK)/extracellular...

A quaternary benzo[c]phenanthridine alkaloid chelerythrine displays a wide range of biological activities including cytotoxicity to normal and cancer cells. In contrast, less is known about the biological activity of dihydrochelerythrine, a product of chelerythrine reduction. We examined the cytotoxicity of chelerythrine and dihydrochelerythrine in human promyelocytic leukemia HL-60 cells. Afte...

Type 2 diabetes mellitus (T2DM) is a pervasive metabolic syndrome that is characterized by insulin resistance, hyperglycemia and dyslipidemia. As full agonists of PPARγ, thiazolidinedione (TZD) drugs elicit antidiabetic effects by targeting PPARγ but is accompanied by weight gain, fluid retention and cardiovascular risk associated with their transcriptional agonism potency. We here identify a n...

Dexmedetomidine, a highly selective α-2 adrenoceptor agonist, produces vasoconstriction, which leads to transiently increased blood pressure. The goal of this study was to investigate specific protein kinases and the associated cellular signal pathways responsible for the increased calcium sensitization induced by dexmedetomidine in isolated rat aortas, with a particular focus on phosphorylatio...