Endophytic fungi from Miquelia dentata Bedd., produce the anti-cancer alkaloid, camptothecine

Abstract

Camptothecine (Campothecin, CPT), a quinoline alkaloid, is a potent inhibitor of eukaryotic topoisomerase I. Several semi-synthetic derivatives of CPT are in clinical use against ovarian, small lung and refractory ovarian cancers. While CPT is produced by several plant species belonging to the Asterid clade, in recent years, efforts have been made to isolate endophytic fungi from some of these plants as possible alternative sources of CPT. In this study we report the isolation of three endophytic fungi from fruit and seed regions of Miquelia dentata (Icacinaceae), that produce CPT, 9-methoxy CPT (9-MeO-CPT) and 10-hydroxy CPT (10-OH-CPT). All the three fungi identified as, Fomitopsis sp. P. Karst (MTCC 10177), Alternaria alternata (Fr.) Keissl (MTCC 5477) and Phomposis sp. (Sacc.) produced CPT, 9-MeO-CPT and 10-OH-CPT in mycelial mats in shake flasks containing potato dextrose broth. Methanolic and ethyl acetate extracts of these fungal species were cytotoxic to colon and breast cancer cell lines. We discuss these results in the context of the recent interest in endophytic fungi as possible alternative sources of plant secondary metabolites.