Choi Hye Joung, Bae Song-Ja, Kim Nam Deuk, Jung Jee H, Choi Yung Hyun
Department of Biochemistry, Dongeui University College of Oriental Medicineand Biomedical Research Center of Oriental Medicine, Busan 614-052, Korea.
Int J Mol Med. 2004 Dec;14(6):1091-6.
Dideoxypetrosynol A, a polyacetylene from the sponge Petrosia sp., is known to exhibit significant selective cytotoxicity against several human tumor cell lines. In the present study, we investigated the possible mechanisms by which dideoxypetrosynol A exerts its anti-proliferative action in cultured human SK-MEL-2 skin melanoma cells. Exposure of SK-MEL-2 cells to dideoxypetrosynol A resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometry analysis. The increase in apoptosis was associated with a dose-dependent up-regulation in proapoptotic Bax expression and down-regulation of anti-apoptotic Bcl-2. Apoptosis-inducing concentrations of dideoxypetrosynol A induced caspase-3 and caspase-9 activation accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase and selective down-regulation of cIAP-1. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of dideoxypetrosynol A.
双脱氧岩藻醇A是一种从海绵Petrosia sp.中提取的聚乙炔，已知其对多种人类肿瘤细胞系具有显著的选择性细胞毒性。在本研究中，我们研究了双脱氧岩藻醇A在培养的人SK-MEL-2皮肤黑色素瘤细胞中发挥抗增殖作用的可能机制。通过MTT法、荧光显微镜和流式细胞术分析检测，将SK-MEL-2细胞暴露于双脱氧岩藻醇A会导致生长抑制并以剂量依赖的方式诱导凋亡。凋亡的增加与促凋亡蛋白Bax表达的剂量依赖性上调和抗凋亡蛋白Bcl-2的下调有关。诱导凋亡浓度的双脱氧岩藻醇A可诱导caspase-3和caspase-9激活，同时伴有聚（ADP-核糖）聚合酶的蛋白水解降解和cIAP-1的选择性下调。综上所述，这些发现为双脱氧岩藻醇A抗癌活性的可能分子机制提供了重要的新见解。
