Sarcophine-Diol Inhibits Expression of COX-2, Inhibits Activity of cPLA₂, Enhances Degradation of PLA₂ and PLC_γ1 and Inhibits Cell Membrane Permeability in Mouse Melanoma B₁₆F₁₀ Cells

摘要

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 PLC_γ1 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 PLC_γ1, 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.