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Sarcophine-diol Inhibits Expression of COX-2, Inhibits Activity of cPLA2, Enhances Degradation of PLA2 and PLC(γ)1 and Inhibits Cell Membrane Permeability in Mouse Melanoma B16F10 Cells

Pawel T Szymanski, Pratik Muley, Safwat A Ahmed, Sherief Khalifa, Hesham Fahmy

Mar Drugs. 2012 Oct;10(10):2166-80.

PMID: 23170076

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 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(γ)1 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(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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP55038272 Sarcophine Sarcophine 55038-27-2 Price
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