Bisindolylmaleimides in anti-cancer therapy - more than PKC inhibitors.
Bisindolylmaleimide derivatives were originally described as protein kinase C inhibitors. However, several studies have shown that bisindolylmaleimides target several other signaling molecules. The review presents bisindolylmaleimide-mediated PKC-dependent and PKC-independent biological effects, such as reversal of MDR and modulation of Wnt signaling through GSK-3b and b-catenin. Importantly, the potent proapoptotic properties of bisindolylmaleimides are also described. Bis-IX appears as the most efficient activator of intrinsic apoptotic pathway and additionally, facilitates extrinsic apoptosis. Presented molecular mechanisms indicate that bisindolylmaleimides could be useful agents in anticancer therapy. They repress uncontrolled proliferation and restore the sensitivity to chemotherapy which allows eradication of cancer cells.
Pajak
B
B
Department of Cell Ultrastructure, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. bepaj@wp.pl
Orzechowska
S
S
Gajkowska
B
B
Orzechowski
A
A
D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008301:Maleimides / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*
D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; C088060:bisindolylmaleimide