title: 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.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Pawel T
authors.initials: PT
authors.lastname: Szymanski
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Pratik
authors.initials: P
authors.lastname: Muley
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
authors.forename: Safwat A
authors.initials: SA
authors.lastname: Ahmed
authors.affiliation: College of Pharmacy, Qatar University, Doha 02713, Qatar.
authors.forename: Sherief
authors.initials: S
authors.lastname: Khalifa
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Hesham
authors.initials: H
authors.lastname: Fahmy
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects*; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism*; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D004224:Diterpenes; C573078:sarcophine-diol; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D054510:Phospholipases A2, Cytosolic; D051966:Phospholipase C gamma