Abstract
Hypersaline environments are known to support diverse fungal species from various orders. The production of secondary metabolites is one of the strategies that fungi adopt to thrive under such extreme environments, bringing up the stress tolerance response. Some such unique secondary metabolites also exhibit clinical significance. The increasing prevalence of drug resistance in cancer therapy demands further exploration of these novel bioactive compounds as cancer therapeutics. In the present study, a total of 31 endophytic fungi harboring inside red, green, and brown marine algae have been isolated and identified. The maximum likelihood analysis and diversity indices of fungal endophytes revealed the phylogenetic relationship and species richness. The genus Aspergillus was found to be the dominating fungus, followed by Cladosporium spp. All the isolated endophytic fungal extracts were tested for their cytotoxicity against HeLa and A431 cancer cell lines. Nine isolates were further analyzed for their cytotoxic activity from the culture filtrate and mycelia extract. Among these isolates, Biscogniauxia petrensis showed potential cytotoxicity with CC50 values of 18.04 and 24.85 μg/ml against HeLa and A431 cells, respectively. Furthermore, the media and solvent extraction optimization revealed the highest cytotoxic active compounds in ethyl acetate extract from the potato dextrose yeast extract broth medium. The compound-induced cell death via apoptosis was 50–60 and 45% when assayed using propidium iodide-live/dead and loss of mitochondrial membrane potential assay, respectively, in HeLa cells. Four bioactive fractions (bioassay-based) were obtained and analyzed using chromatography and spectroscopy. This study reports, for the first time, the cytotoxic activity of an endophytic fungal community that was isolated from marine macro-algae in the Rameswaram coastal region of Tamil Nadu, India. In addition, B. petrensis is a prominent apoptotic agent, which can be used in pharmaceutical applications as a therapeutic.
Highlights
Cancer is one of the major causes of illness and death globally (Nagai and Kim, 2017)
The results indicated that the remaining fractions obtained from mycelia extract (16) and culture extract (12) showed a prominent cytotoxic activity against the cancer cells used in this study and exhibited toxic effects on non-cancerous cells (HEK)
31 endophytic fungal strains were isolated from 18 different host algae that were collected from under-explored marine habitats of Gulf of Mannar at Rameswaram to find out their cytotoxic potential
Summary
Cancer is one of the major causes of illness and death globally (Nagai and Kim, 2017). The most extensively used treatment is chemotherapy; the routine use of chemically synthesized anticancer drugs suppresses the immune system. This necessitates the development of anticancer drugs which can control cancer progression in a better way. The discovery of new drugs from natural sources has been the focus of research works (Wright, 2019). In this context, marine fungi are being considered as a new and promising source of bioactive compounds (Deshmukh et al, 2018)
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