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

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 fin...

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Published in:Marine drugs 2012-10, Vol.10 (10), p.2166-2180
Main Authors: Szymanski, Pawel T, Muley, Pratik, Ahmed, Safwat A, Khalifa, Sherief, Fahmy, Hesham
Format: Article
Language:English
Subjects:
Animals
Anthozoa - chemistry
Anthozoa - metabolism
Antineoplastic Agents - pharmacology
Cell Line, Tumor
Cell Membrane Permeability - drug effects
Cell Proliferation
Cyclooxygenase 2 - genetics
Cyclooxygenase 2 - metabolism
Cyclooxygenase 2 Inhibitors - pharmacology
Diterpenes - chemistry
Diterpenes - metabolism
Diterpenes - pharmacology
Gene Expression Regulation, Enzymologic
Melanoma - metabolism
Mice
Molecular Structure
Phospholipase C gamma - genetics
Phospholipase C gamma - metabolism
Phospholipases A2, Cytosolic - antagonists & inhibitors
Phospholipases A2, Cytosolic - metabolism
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Summary: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.
ISSN:1660-3397
DOI:10.3390/md10102166