Cytotoxic Potential of Bioactive Compounds from Aspergillus flavus, an Endophytic Fungus Isolated from Cynodon dactylon, against Breast Cancer: Experimental and Computational Approach.

Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants and exhibit mutual benefits. Their interactions with the host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. An in vitro analysis of the Ethyl acetate extract from A. flavus showed significant cytostatic effects (IC50: 16.25 µg/mL) against breast cancer cells (MCF-7). A morphological analysis of the cells and a flow cytometry of the cells with annexin V/Propidium Iodide suggested that the extract induced apoptosis in the MCF-7 cells. The extract of A. flavus increased reactive oxygen species (ROS) generation and caused a loss of mitochondrial membrane potential in MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was subjected to a gas chromatography-mass spectrometry (GC-MS) analysis. Interestingly, nine phytochemicals that induced cytotoxicity in the breast cancer cell line were found in the extract. The in silico molecular docking and molecular dynamics simulation studies revealed that two compounds, 2,4,7-trinitrofluorenone and 3α, 5 α-cyclo-ergosta-7,9(11), 22t-triene-6beta-ol exhibited significant binding affinities (-9.20, and -9.50 Kcal/mol, respectively) against Bcl-2, along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer.

Exopolysaccharides from Lactobacillus acidophilus modulates the antioxidant status of 1,2-dimethyl hydrazine-induced colon cancer rat model.

The aim of the current study is to ascertain the anticancer activity of exopolysaccharides (EPS) from probiotic Lactobacillus acidophilus in the 1, 2-dimethyl hydrazine (DMH)-induced colon cancer rat model and to determine the antioxidant status. Rats were divided into five groups of six animals each. Group I served as control, group II served as cancer control (DMH alone administered), group III as standard drug control (5-FU along with DMH) and group IV and V received EPS in two doses (200 mg/kg body weight and 400 mg/kg body weight along with DMH). EPS administration was found to reduce the number of polyps formed (Group IV-8.25 ± 1.258 and Group V-8.50 ± 1.732 vs Group II-14.50 ± 2.380) and to increase the levels of antioxidant enzymes viz. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and antioxidants like vitamin C (Vit. C), reduced glutathione (GSH) which was found to be reduced in colon cancer control rats. The status of lipid peroxidation (LPO) was also evaluated. All the values which were affected by the supplementation of DMH were brought to near normal levels by the treatment with EPS. The well-preserved histology of colon and the biochemical evaluation also show that EPS could be a potential agent for the prevention and treatment of colon cancer.