A novel adriamycin analogue derived from marine microbes induces apoptosis by blocking Akt activation in human breast cancer cells

作者：Yuan, Jie; He, Zhenjian; Wu, Jueheng; Lin, Yongcheng; Zhu, Xun^*

来源：Molecular Medicine Reports, 2011, 4(2): 261-265.

DOI：10.3892/mmr.2011.434

• marine
• adriamycin analogue
• breast cancer
• apoptosis
• Akt

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 mu M, respectively. Apoptosis induced by 1403P-3 was detected, as indicated by Annexin V-FITC/P1 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.

• 出版日期2011-3
• 单位中山大学