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  • Title: The antiproliferative effect of spectinabilins from Streptomyces spectabilis on hepatocellular carcinoma cells in vitro and in vivo.
    Author: Gao X, Yao H, Mu Y, Guan P, Li G, Lin B, Jiang Y, Han L, Huang X, Jiang C.
    Journal: Bioorg Chem; 2019 Dec; 93():103311. PubMed ID: 31586709.
    Abstract:
    Spectinabilin (1), spectinabilin derivative (2), and a new analogue, 2-demethyl-spectinabilin (3) were isolated from the fermentation broth of a soil-borne Streptomyces spectabilis strain. The structure of the new compound was elucidated by a detailed spectroscopic data analysis including data from CD spectra. Spectinabilin (1) demonstrated cytotoxicity against five human cancer cell lines, with IC50 values ranging from 18.7 ± 3.1 to 34.6 ± 4.7 μM, while derivatives 2 and 3 showed weak cytotoxicities. Notably, 1 inhibited the growth and proliferation of the hepatocellular carcinoma cell lines SMMC7721 and HepG2 in a time- and dose-dependent manner. Further study demonstrated that 1 caused G2/M phase cell cycle arrest in SMMC7721 and HepG2 cells through decreasing the protein levels of cyclin B1 and cdc2 as well as increasing that of p21. Compound 1 downregulated the protein expression of Bcl-2, upregulated Bax, and activated the cleavage of caspase-9 and -3 as a result of inducing apoptosis in SMMC7721 and HepG2 cells. Furthermore, the antitumor effect of 1 in SMMC7721 and HepG2 cells was mediated by the PI3K/AKT signaling pathway. In addition, 1 also suppressed tumor growth in vivo though inducing cell cycle arrest and apoptosis.
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