Fungal Secondary Metabolites: A Promising Source of Antineoplastic Drugs

The rapid progress in understanding the molecular biology of cancer has made a large impact on the design and development of novel therapeutic strategies prompted by the multi-factorial limitations of the current chemotherapeutic modalities. Given that the development of newer antineoplastic drugs continues to rely heavily on isolation from natural sources rather than applications based on rational drug design and combinatorial chemistry, fungal secondary metabolites rank high on the list of potential targets for the discovery of novel chemotherapeutic agents. They represent a diverse group of bioactive compounds characterized by their origin and biosynthetic pathways. Also, they serve as regulators, chemical messengers in developmental processes, or as antibiotics. A broad variety of fungal secondary metabolites possess potent antitumor activity. Alpha sarcin, gliotoxins, trichodimerol, L-lysine alpha-oxidase, fumagillin, declauxin, chrysanthones, fungal-derived low molecular weight inhibitors of angiogenesis e.g. TNP- 470, retamycin, daunorubicin, and doxorubicin all have been shown to exert potent antitumor activity. Inhibition of protein synthesis, induction of DNA breakage and apoptosis, as well as blockade of angiogenesis are examples of the multiple antitumor mechanisms of fungal secondary metabolites. The current review explores the potential use of fungal secondary metabolites as antineoplastic drugs with special reference to the novel hepatoma growth-inhibition factor that we recently characterized from Trichoderma viride.