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

Marine Drugs

Pawel T. Szymanski¹  Pratik Muley¹  Safwat A. Ahmed²  Sherief Khalifa³ 

[1] Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA;Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt;College of Pharmacy, Qatar University, Doha 02713, Qatar;

关键词: melanoma;    sarcophine;    sarcophine-diol;    skin cancer;    melanoma;   

DOI  :  10.3390/md10102166

来源: mdpi

【 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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.