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.
Mar Drugs. 2012 Oct;10(10):2166-2180. doi: 10.3390/md10102166. Epub 2012 Sep 28.
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.
鲨肌醇二醇（SD）是鲨肌醇的半合成衍生物，具有显著的化学预防作用，可预防非黑色素瘤皮肤癌的发生，无论是在体外还是体内。最近，我们使用小鼠黑色素瘤 B₁₆F₁₀ 细胞系研究了 SD 对黑色素瘤发展的影响。在这项研究中，我们的发现表明 SD 抑制细胞增殖并降低溴化乙锭（EB）的膜通透性，EB 是一种用于测量 Ca²⁺离子细胞通透性的模型标志物。SD 还降低 COX-2 的蛋白水平，增加磷脂酶 PLA₂ 和 PLC(γ)1 的降解，并降低 Ca²⁺依赖性 cPLA₂ 的酶活性。与 SD 相关的 Ca²⁺离子较低的膜通透性，很可能是由于 SD 对 PLA₂ 的作用导致细胞膜内溶血磷脂酰胆碱（lysoPC）含量减少所致。由于 PLC(γ)1 的抑制，二酰甘油（DAG）和肌醇 1,4,5-三磷酸（IP₃）的减少导致细胞内 Ca²⁺依赖性过程的下调，并抑制肿瘤的形成。这些发现支持了我们之前的数据，表明 SD 可能在治疗黑色素瘤方面具有重要的潜力。
