Evaluation of Antiangiogenic and Antimetastatic Effects of Penicillium chrysogenum Secondary Metabolites

Abstract

Development of resistance to standard therapy and toxic side effects are the major challenges encountered in chemotherapy of colorectal cancer. Increasing evidence has shown the ability of natural products to overcome various challenging disorders. Since, the development of antibiotics, fungi have been shown to be a wide useful source of lead compounds for the development of new pharmaceuticals. Fungal secondary metabolites from extreme environments are remarkable due to their diverse components, which makes them interesting candidates for drug discovery. In order to discover novel active antimetastatic and antiangiogenic compounds, secondary metabolites of halotolerant Penicillium chrysogenum-1 isolated from Tuz Lake in Turkey and ethyl acetate extract of halotolerant P. chrysogenum-1 was prepared from the isolate of halotolerant P. chrysogenum-1 culture medium. Firstly, antioxidant activity of the extract was determined. Then cytotoxicity and cell proliferation were investigated by WST-1 assay and real-time cell analysis system-DP on human umbilical vein endothelial cells and colorectal carcinoma cells, respectively. Antiangiogenic effects on human umbilical vein endothelial cells were evaluated with cell migration and invasion assays by using real-time cell analysis system. Also, mRNA expression levels of metastasis and angiogenesis-related genes, VEGFA, VEGFB, EGFR, COX-10, ANGPT-1 and IL-8 were determined on both cell lines. Results indicated that halotolerant P. chrysogenum-1 extract exhibited significant antimetastatic and antiangiogenic effects. According to the real-time cell analysis system results, IC50 concentrations of halotolerant P. chrysogenum-1 extract on Caco-2 and human umbilical vein endothelial cells were calculated as 55.2 and 37.89 mu g/ml, respectively for 72 h. These results indicated that the secondary metabolites of halotolerant P. chrysogenum-1 extract could have the potential as a preventive and therapeutic agent in metastatic cancer processes.