In-vitro, In-silico Investigations Reveals Potential Cytotoxic Activity of Fermentation Metabolites from Actinomycetes Isolated from Lonar Soda Lake Against HeLa Cancer Cell Lines.

Background: Actinomycetes, Gram-positive bacteria, are recognized for producing bioactive metabolites. Lonar Soda Lake, an alkaline ecosystem, hosts diverse actinomycetes with possible anticancer activities.

Aim: To assess the cytotoxic potential of fermentation metabolites from actinomycetes isolated from Lonar Soda Lake against HeLa cancer cells employing in-vitro and in-silico methods.

Objectives: Evaluate the cytotoxicity of fermentation metabolites from Lonar Lake actinomycetes on HeLa cells. Execute molecular docking to forecast metabolite connections with cancer-related proteins.

Materials and methods: The actinomycetes were isolated from the sediment sample of Lonar Lake using a selective medium and recognized by gene sequencing. Cytotoxicity on HeLa cells was assessed using the MTT assay, in consort with oxidative stress and apoptotic markers (GSH, MDA, TNF-α, and caspase 3). Molecular docking and molecular dynamics studies evaluated metabolite binding to cancer-related proteins (Bcl-2, TNF-α, caspase 3).

Results: Fermentation metabolites of three Lonar Lake Sediment isolates (LLSD), LLSD-5, LLSD- 7, and LLSD-9 showing promising cytotoxic activity against HeLa cell lines by MTT assay, also significantly modulate the oxidative stress parameters (GSH, MDA), and cell apoptotic marker (TNF-α, caspase 3). IC50 values were 82.9 μg/ml (LLSD-5), 162.3 μg/ml (LLSD-7), and 20.15 μg/ml (LLSD-9). Furthermore, molecular docking displayed robust binding affinities to cancer-related proteins, uncovering the possible mechanism of action.

Conclusion: The fermentation metabolites actinomycete isolates from Lonar Lake exhibit significant cytotoxic activity against HeLa cancer cell lines. Both in-vitro and in-silico analyses support the potential of these metabolites as anticancer agents.