来自吕宋棘冠海星的吕宋糖苷对人黑色素瘤细胞的抑制活性。

The Inhibitory Activity of Luzonicosides from the Starfish Echinaster luzonicus against Human Melanoma Cells.

作者信息

Malyarenko Olesya S, Dyshlovoy Sergey A, Kicha Alla A, Ivanchina Natalia V, Malyarenko Timofey V, Carsten Bokemeyer, Gunhild von Amsberg, Stonik Valentin A, Ermakova Svetlana P

机构信息

Laboratory of Enzyme Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch, Russian Academy of Sciences, Vladivostok 690022, Russia.

Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch, Russian Academy of Sciences, Vladivostok 690022, Russia.

出版信息

Mar Drugs. 2017 Jul 18;15(7):227. doi: 10.3390/md15070227.

Malignant melanoma is the most dangerous form of skin cancer, with a rapidly increasing incidence rate. Despite recent advances in melanoma research following the approval of several novel targeted and immuno-therapies, the majority of oncological patients will ultimately perish from the disease. Thus, new effective drugs are still required. Starfish steroid glycosides possess different biological activities, including antitumor activity. The current study focused on the determination of the in vitro inhibitory activity and the mechanism of action of cyclic steroid glycosides isolated from the starfish -luzonicoside A (LuzA) and luzonicoside D (LuzD)-in human melanoma RPMI-7951 and SK-Mel-28 cell lines. LuzA inhibited proliferation, the formation of colonies, and the migration of SK-Mel-28 cells significantly more than LuzD. Anti-cancer activity has been ascribed to cell cycle regulation and apoptosis induction. The molecular mechanism of action appears to be related to the regulation of the activity of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP), along with Survivin, Bcl-2, p21 and cyclin D1 level. Overall, our findings support a potential anti-cancer efficacy of luzonicosides A and D on human melanoma cells.

恶性黑色素瘤是最危险的皮肤癌形式，其发病率正在迅速上升。尽管在几种新型靶向疗法和免疫疗法获批后，黑色素瘤研究取得了最新进展，但大多数肿瘤患者最终仍会死于该疾病。因此，仍需要新的有效药物。海星甾体糖苷具有不同的生物活性，包括抗肿瘤活性。当前的研究聚焦于从海星中分离出的环状甾体糖苷——卢佐糖苷A（LuzA）和卢佐糖苷D（LuzD）——对人黑色素瘤RPMI - 7951和SK - Mel - 28细胞系的体外抑制活性及作用机制的测定。LuzA对SK - Mel - 28细胞增殖、集落形成及迁移的抑制作用明显强于LuzD。抗癌活性归因于细胞周期调控和凋亡诱导。其分子作用机制似乎与裂解的半胱天冬酶 - 3和聚（ADP - 核糖）聚合酶（PARP）的活性调节有关，同时还与生存素、Bcl - 2、p21和细胞周期蛋白D1的水平有关。总体而言，我们的研究结果支持卢佐糖苷A和D对人黑色素瘤细胞具有潜在的抗癌疗效。