The antiproliferative effect of spectinabilins from Streptomyces spectabilis on hepatocellular carcinoma cells in vitro and in vivo

[Display omitted] •One new spectinabilin and two known analogues were isolated from S. spectabilis.•Spectinabilin suppressed the tumor growth in SMMC7721 xenografted mice.•Spectinabilin caused cell cycle arrest by regulating cyclin B1, cdc2 and p21.•Spectinabilin induced apoptosis in HCC cells by activating the caspase-9 and -3.•The effect of Spectinabilin was mediated by PI3K/AKT signaling pathway. 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.