Antitumor Activity of Ohmyungsamycin A through the Regulation of the Skp2-p27 Axis and MCM4 in Human Colorectal Cancer Cells.

Ohmyungsamycin A (), a novel cyclic peptide discovered from a marine sp., was previously reported with antibacterial and anticancer activities. However, the antitumor activities and the underlying molecular mechanisms of remain to be elucidated. Compound inhibited the proliferation and tumor growth of HCT116 human colorectal cancer cells based on both cell cultures and an animal model. A cDNA microarray analysis revealed that downregulated genes involved in cell cycle checkpoint control. Compound also induced G/G cell cycle arrest that was mediated by the regulation of S-phase kinase-associated protein 2 (Skp2)-p27 axis and minichromosome maintenance protein 4 (MCM4). Furthermore, a longer exposure of exhibited an accumulation of a sub-G phase cell population, which is characteristic of apoptotic cells. The induction of apoptosis by was also associated with the modulation of caspase family proteins. Compound effectively suppressed tumor growth in a xenograft mouse model subcutaneously implanted with HCT116 cells. In addition, analysis of tumors revealed that upregulated the expression of the CDK inhibitor p27 but downregulated the expression of Skp2 and MCM4. These findings demonstrate the involvement of in cell cycle regulation and the induction of apoptosis in human colorectal cancer cells.