In this study, anti-proliferative effects of isosclerone, isolated from a marine-derived fungus, Aspergillus fumigatus was studied in vitro. The isosclerone showed significant cytotoxicity toward MCF-7 human breast cancer cells at the concentration of 60 mu M after 24 h incubation. Further, isosclerone inhibited the protein and gene level expressions of MMP-2,-9 in a dose-dependent manner in MCF-7 human breast cancer cells via attenuating MAPK signaling pathway molecules. The cell cycle analysis results indicated the apoptosis inducing effects of isosclerone and to explore the underlying mechanism, we examined the effects of isosclerone on the expression of cell cycle regulatory proteins; CDK2, CDK4, cyclin BI and cyclin E. Moreover, isosclerone has significantly up-regulated the p53 gene at the transcriptional level. These results suggest that isosclerone would be a useful compound in developing therapeutics for breast cancer. (C) 2014 Elsevier Ltd. All rights reserved.