Fungal endophytes: an untapped natural products source of cytotoxic agents

Abstract

Endophytes are microorganisms that live within the intercellular space of almost all vascular plants. Endophytes benefit their hosts by producing bioactive secondary metabolites that prevent invasion by pathogenic agents. Endophytic metabolites that specifically kill plant‐pathogenic or other competing microorganisms might also have bioactive or cytotoxic effects in humans, and thus represent a potential source of medicinal compounds. It is estimated that 95% of fungal endophytes remain undiscovered and unexplored. In the present study, fungal endophytes were isolated from medicinal plants collected from locations within the central valley area of California. The plants were plated onto potato dextrose agar plates under aseptic conditions and incubated at 28°C in the dark until endophyte isolates emerged. Each endophyte was then grown in potato dextrose broth at 28°C until sufficient fungal mass was obtained. Cytotoxicity of the endophyte culture media was then assessed by formazan precipitation assay in Hep3B cells (human hepatocellular carcinoma) and rat hepatocytes. Among 25 endophyte cultures tested, 15TWA01 from blue gum (Eucalyptus globules) showed 60‐92% and 20‐60% cytotoxicity in Hep3B cells and rat hepatocytes, respectively. Future studies will determine the cytotoxic component(s) of the 15TWA01 culture, as well as the mechanism of cytotoxicity.