Abstract
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&sub1;₆F&sub1;&sub0; 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 PLA&sub2; and PLC(γ)1 and diminishes enzymatic activity of the Ca²⁺-dependent cPLA&sub2;. 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 PLA&sub2;. The decrease in diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP&sub3;) due to inhibition of PLC(γ)1, 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.