Evaluation of Antiangiogenic and Antimetastatic Effects of Penicillium chrysogenum Secondary Metabolites

Abstract

Dikmen, et al.: Antiangiogenic and Antimetastatic Effects of Penicillium chrysogenumDevelopment 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, IC 50 concentrations of halotolerant P. chrysogenum-1 extract on Caco-2 and human umbilical vein endothelial cells were calculated as 55.2 and 37.89 µg/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.

In Vitro Efficacy of Extracts and Isolated Bioactive Compounds from Ascomycota Fungi in the Treatment of Colorectal Cancer: A Systematic Review

“…The most relevant studies in the genus Penicillium used the ethyl acetate extraction method (five out of fourteen) [ 22 , 32 ] or methanol and ethanol methods (two out of fourteen) [ 49 , 54 , 56 ] to develop functional extracts that showed IC 50 values between 0.2 and 102 µg/mL in CRC cells. Canturk et al [ 56 ] and Dikmen et al [ 38 ] showed that ethyl acetate extracts reduced the invasiveness of cancer cells by decreasing cell migration and the expression of genes related to angiogenesis and metastasis.…”

Proteasome Inhibitor Immunotherapy for the Epithelial to Mesenchymal Transition: Assessing the A549 Lung Cancer Cell Microenvironment and the Role of M1, M2a and M2c ‘Hydrocortisone-Polarised’ Macrophages

“…All assays were performed in 8 wells, and the average values were calculated. Cell proliferation and IC 50 concentrations of bortezomib and ixazomib were monitored and evaluated for 48 h according to the CI values by RTCA DP Software 1.2.1 [15,16] Co-culture procedures THP-1 polarised macrophages were co-cultured with A549 lung cancer cells in indirect contact via transwell inserts (Corning, NY, USA) to investigate the impact of M1, M2a and M2c on cancer cell sensitivity to proteasome inhibitors. The A549 cells were co-cultured with M1, M2a, and M2c macrophages in six-well plate cell culture inserts with a 0.4-m porous membrane separating the upper and lower chambers, allowing for the exchange of soluble factors but not cell transmigration.…”

“…RTCA DP detects the cell number indirectly by measuring electrical impedance and generates real-time data by collecting measurements at predetermined intervals over a period of days [14][15][16]. In our study, the RTCA DP system was used for the real-time and time-dependent analysis of IC 50 concentrations of A549 and CCD-19Lu cells.…”

Evaluation of Real Time Cell Proliferation, Anti-Inflammatory and Wound Healing Potential of Helenalin on HaCaT Keratinocytes Treated with Lipopolysaccharide Stimulated Monocytes

“…The stimulated medium (+LPS) was used as a control group. After stabilizing the CIM plates for 30 min at room temperature, the chamber was loaded into the RTCA DP machine and software was set to collect impedance data, reported as CI values, once every 10 min for 24 h [32,41] .…”