title: Induction of apoptosis against cancer cell lines by four ascomycetes (endophytes) from Malaysian rainforest.
abstract: Endophytic fungi have been shown to be a promising source of biologically active natural products. In the present study, extracts of four endophytic fungi isolated from plants of the National Park, Pahang were evaluated for their cytotoxic activity and the nature of their active compounds determined. Those extracts exhibiting activity with IC(50) values less than 17 μg/ml against HCT116, MCF-7 and K562 cell lines were shown to induce apoptosis in these cell lines. Molecular analysis, based on sequences of the rDNA internal transcribed spacers ITS1 and ITS4, revealed all four endophytic fungi to be ascomycetes: three sordariomycetes and a dothideomycete. Six known compounds, cytochalasin J, dechlorogriseofulvin, demethylharzianic-acid, griseofulvin, harzianic acid and 2-hexylidene-3-methyl-succinic acid were identified from a rapid dereplication technique for fungal metabolites using an in-house UV library. The results from the present study suggest the potential of endophytic fungi as cytotoxic agents, and there is an indication that the isolates contain bioactive compounds that mainly kill cancer cells by apoptosis.
authors.affiliation: Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Nurul Aqmar Mohamad Nor
authors.initials: NA
authors.lastname: Hazalin
authors.forename: Kalavathy
authors.initials: K
authors.lastname: Ramasamy
authors.forename: Siong Meng
authors.initials: SM
authors.lastname: Lim
authors.forename: Anthony L J
authors.initials: AL
authors.lastname: Cole
authors.forename: Abu Bakar Abdul
authors.initials: AB
authors.lastname: Majeed
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001203:Ascomycota / Q000737:chemistry* / Q000235:genetics; D001483:Base Sequence; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004271:DNA, Fungal / Q000032:analysis; D021903:DNA, Ribosomal Spacer / Q000032:analysis; D060026:Endophytes / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D008296:Malaysia; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D011891:Rain; D014197:Trees
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D004271:DNA, Fungal; D021903:DNA, Ribosomal Spacer