Exploring the Marine Algicolous Endophytic Fungi: A Promising Source of Novel Cancer Therapeutics

Abstract

Cancer is the second leading cause of mortality globally, with over 6 million new cases diagnosed annually. Research on effective therapies is crucial due to the disease's complexity. Natural materials in chemotherapy have shown potential. Marine ecosystems are a source of pharmaceutically relevant secondary metabolites, including anticancer drug leads and antivirals. Endophytic fungi are an important source of these compounds, as they are abundant in marine habitats and are being evaluated as potential anticancer treatment leads by the pharmaceutical sector. In the current study, 31 endophytic fungi have been isolated from marine algae, inhabitants of the Bay of Bengal. Their identification by ITS sequencing revealed Aspergillus spp. as the most prevalent among 17 genera, followed by Cladosporium spp. Nine obtained fungus extracts demonstrated appreciable cytotoxicity when their cytotoxicity was evaluated against HeLa and A431 cell lines. A rarely reported endophytic fungus called Biscogniauxia petrensis was isolated from the green macroalga Halimeda macroloba, collected from the Bay of Bengal, shown highest cytotoxicity with IC50 concentration 18.04 and 24.85 µg/ml for HeLa and A431 cells, respectively. The potato dextrose yeast extract broth medium and semi-polar solvent ethyl acetate supported the production as well as extraction of cytotoxic metabolites from B. petrensis in a higher quantity. The chemicals (C2 and M4) that were column-purified inhibited growth of HeLa cells by stopping the cell cycle at the Sub-G1 phase and eventually induced apoptotic cell death by various mechanism, includes loss of membrane integrity, DNA damage, ROS production, loss of mitochondrial potential leading to release of specific proteins/factors such as cytC, Apaf-1. Caspase activation finally executed the signaling involving both extrinsic and intrinsic pathway. We have also addressed the synthesis of oxalic acid dihydrate, by three Aspergillus spp., isolated from marine macro-algae. Being a potent inhibitor of the enzyme lactate dehydrogenase (LDH), oxalic acid dihydrate offers an intriguing method to stop the development of tumors, as tumor cells are highly dependent on the lactate fermentation for the energy metabolism, and LDH plays the key role, which explain the importance of fungal compounds in targeted therapy for cancer. Additional experiments by chemical modification, we have successfully increased the efficacy of fungal oxalic acid by 45%, increasing. All together our finding exposes the marine endophytic fungi as a sustainable source of complex and novel chemical entities having potent anti-cancer properties.