title: A novel adriamycin analogue derived from marine microbes induces apoptosis by blocking Akt activation in human breast cancer cells.
abstract: 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.
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou 510080, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.forename: Zhenjian
authors.initials: Z
authors.lastname: He
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Lin
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives*; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005658:Fungi / Q000737:chemistry*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012623:Seawater / Q000382:microbiology*
chemical_list: C529129:1403P-3 compound; D000880:Anthraquinones; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053181:Caspase 8; D053453:Caspase 9