Sarcophine-Diol Inhibits Expression of COX-2, Inhibits Activity of cPLA2, Enhances Degradation of PLA2 and PLCγ1 and Inhibits Cell Membrane Permeability in Mouse Melanoma B16F10 Cells
2012
Pawel T. Szymanski | Pratik Muley | Safwat A. Ahmed | Sherief Khalifa | Hesham Fahmy
Sarcophine-diol (SD) is a semi-synthetic derivative of sarcophine with a significant chemopreventive effect against non-melanoma skin cancer both in vitro and in vivo. Recently, we have studied the effect of SD on melanoma development using the mouse melanoma B16F10 cell line. In this study, our findings show that SD suppresses cell multiplication and diminishes membrane permeability for ethidium bromide (EB), a model marker used to measure cell permeability for Ca2+ ions. SD also decreases protein levels of COX-2, and increases degradation of phospholipases PLA2 and PLCγ1 and diminishes enzymatic activity of the Ca2+-dependent cPLA2. This lower membrane permeability for Ca2+-ions, associated with SD, is most likely due to the diminished content of lysophosphosphatidylcholine (lysoPC) within cell membranes caused by the effect of SD on PLA2. The decrease in diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3) due to inhibition of PLCγ1, leads to the downregulation of Ca2+-dependent processes within the cell and also inhibits the formation of tumors. These findings support our previous data suggesting that SD may have significant potential in the treatment of melanoma.
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