Sarcophine-Diol Inhibits Expression of COX-2, Inhibits Activity of cPLA(2), Enhances Degradation of PLA(2) and PLC(γ)1 and Inhibits Cell Membrane Permeability in Mouse Melanoma B(16)F(10) Cells

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 B(16)F(10) 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 Ca(2+) ions. SD also decreases protein levels of COX-2, and increases degradation of phospholipases PLA(2) and PLC(γ)1 and diminishes enzymatic activity of the Ca(2+)-dependent cPLA(2). This lower membrane permeability for Ca(2+)-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 PLA(2). The decrease in diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP(3)) due to inhibition of PLC(γ)1, leads to the downregulation of Ca(2+)-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.