Inhibitory effects of secondary metabolites of halotolerant Aspergillus terreus on angiogenesis.

Abstract

Angiogenesis inhibitors have been currently developed which offer the hope of new treatment options such as diabetic retinopathy, psoriasis, rheumatoid arthritis and cancer. Fungi have been known (as) a wide useful source of antiangiogenic compounds for the development of new pharmaceuticals. Especially, fungal secondary metabolites from extreme environments are remarkable due to their diverse components, which make them interesting candidates for new drug discovery. In this study, in order to discover novel active antiangiogenic compounds, secondary metabolites of halotolerant Aspergillus terreus-2 (hAt-2) were isolated from Tuz Lake in Turkey and ethylacetate extract of hAt-2 was prepared from the isolate of hAt-2 culture medium. Cytotoxicity and cell proliferations were investigated by WST-1 assay and Real-Time Cell Analysis system (RTCA-DP) on Human Umbilical Vein Endothelial Cells (HUVECs). Antiangiogenic effects of the extract on HUVEC cells were evaluated with cell migration and invasion assays by using RTCA-DP analysis which is a new electrical impedance method. Antiproliferative effects of the extract were increased on HUVECs depending on concentration and time and, IC50 value was calculated as 42.13 mu g/ml. In the invasion and migration assays, 50 and 200 mu g/ml concentrations of the extract were significantly suppressed angiogenic responses on HUVEC. According to our results, hAt-2 extract exhibited significant antiangiogenic effects on HUVEC cells. This finding suggests that hAT-2 extract might be pharmacologically active and the secondary metabolites of hAt-2 extract may have potential as a preventive and therapeutic agent on angiogenesis.