A novel adriamycin analogue derived from marine microbes induces apoptosis by blocking Akt activation in human breast cancer cells.
A novel adriamycin analogue derived from marine microbes induces apoptosis by blocking Akt activation in human breast cancer cells.
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DOI：
10.3892/mmr.2011.434
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发表时间：
2011-03
影响因子：
3.4
通讯作者：
Jie Yuan;Zhenjian He;Jueheng Wu;Yongcheng Lin;Xun Zhu
中科院分区：
文献类型：
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作者：
Jie Yuan;Zhenjian He;Jueheng Wu;Yongcheng Lin;Xun Zhu
1403P-3是一种从南海内生真菌次生代谢产物中分离得到的新型蒽二酮衍生物。在以往的研究中，发现1403P-3对人类癌细胞表现出强大的细胞毒性，但其分子靶点和介导其细胞毒性的机制尚不清楚。在这项研究中，我们发现1403P-3以剂量依赖的方式显着抑制人乳腺癌细胞MCF-7和MDA-MB-435的存活，IC₅0分别为9.5和7.6µM。Annexin V-FITC/PI染色显示1403P-3诱导凋亡，Western blot检测活化caspase-8和-9升高，裂解PARP。值得注意的是，在1403p -3处理的细胞中，Akt的磷酸化水平显著降低，并呈剂量和时间依赖性。综上所述，我们的数据表明1403P-3通过阻断Akt的激活诱导乳腺癌细胞凋亡，这表明1403P-3可能是一种有前景的抗肿瘤药物开发候选化合物。
1403P-3 is a novel anthracenedione derivative isolated from the secondary metabolites of endophytic fungus from the South China Sea. In previous studies, 1403P-3 was found to exhibit potent cytotoxicity against human cancer cells, but its molecular target and the mechanisms mediating its cytotoxicity remain unknown. In this study, we showed that 1403P-3 markedly inhibited the survival of the human breast cancer cells MCF-7 and MDA-MB-435 in a dose-dependent manner, with an IC₅₀ of 9.5 and 7.6 µM, respectively. Apoptosis induced by 1403P-3 was detected, as indicated by Annexin V-FITC/PI staining, elevated activated caspase-8 and -9, and cleavaged PARP determined by Western blot analysis. It is of note that the phosphorylation level of Akt was significantly reduced in 1403P-3-treated cells in a dose- and time-dependent manner. Taken together, our data demonstrated that 1403P-3 induced breast cancer cell apoptosis by blocking Akt activation, suggesting that 1403P-3 may be a promising candidate compound for anti-tumor drug development.