Isolation and biological properties of novel cell cycle inhibitors, HY558, isolated from Penicillium minioluteum F558

Abstract

In the course of screening for a novel cell cycle inhibitor, a potent Cdk 1 inhibitor, HY558, was found from the culture broth of Penicillium minioluteum F558 isolated from a soil sample. The molecular ion of HY558 was identified at m/z 329 (MH+) with a molecular formula of C20H44ON2. HY558 exhibited selective antiproliferative effects on various human cancer cell lines. Its IC50 values were estimated to be 0.29 mM on HepG2, 0.30 mM on HeLa, 0.30 mM on HL60, 0.33 mM on HT-29, and 0.25 mM on AGS cells. Interestingly, HY558 demonstrated no antiproliferative effect with normal lymphocytes used as the control, and a low level of inhibition on the proliferation of A549 cancer cells. A flow cytometric analysis of HepG2 cells revealed an appreciable arrest of cells at the G1 and G2/M phases of the cell cycle following treatment with HY558. Furthermore, DNA fragmentation due to apoptosis was observed in HeLa cells treated with 0.46 mM of HY558.