Lee Ji-Hyeon, Park Sang Eun, Hossain Mohammad Akbar, Kim Min Young, Kim Mi-Na, Chung Hae Young, Choi Jae Sue, Yoo Young Hyun, Kim Nam Deuk
Division of Pharmacy (BK21 Program), College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan 609-735, Korea.
Arch Pharm Res. 2007 Sep;30(9):1132-7. doi: 10.1007/BF02980248.
In this study, we investigated the effects of 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (TDB), isolated from Symphyocladia latiuscula (marine red algae), on the proliferation of MCF-7 human breast cancer cells. TDB treatment for 48 h inhibited cancer cell growth and induced DNA fragmentation. Furthermore, morphological characterizations such as apoptotic bodies and membrane blebs were shown by electronic microscopy. TDB-induced apoptosis in the MCF-7 cells was closely linked with the down-regulation of Bcl-2 protein expression and the cleavage of caspase-3 substrates, with poly(ADP-ribose) polymerase cleavage occurring by TDB treatment. TDB treatment also caused a marked increase in the level of p21WAF1/CIP1 protein in a p53-dependent manner. In addition, the upregulation of p21WAF1/CIP1 in the MCF-7 cells was related to a decrease in c-Myc protein in a dose-dependent manner. Based on our data, TDB is a good candidate for further evaluation as an effective chemotherapeutic agent, acting through the induction of apoptosis.
在本研究中，我们研究了从宽叶叉枝藻（一种海洋红藻）中分离出的2,3,6-三溴-4,5-二羟基苄基甲基醚（TDB）对MCF-7人乳腺癌细胞增殖的影响。TDB处理48小时可抑制癌细胞生长并诱导DNA片段化。此外，电子显微镜显示出凋亡小体和细胞膜泡等形态学特征。TDB诱导MCF-7细胞凋亡与Bcl-2蛋白表达下调和caspase-3底物的裂解密切相关，TDB处理会导致聚（ADP-核糖）聚合酶裂解。TDB处理还以p53依赖的方式导致p21WAF1/CIP1蛋白水平显著增加。此外，MCF-7细胞中p21WAF1/CIP1的上调与c-Myc蛋白的剂量依赖性降低有关。基于我们的数据，TDB作为一种有效的化疗药物，通过诱导凋亡发挥作用，是进一步评估的良好候选药物。
