title: Endophytic fungi associated with Taxus fuana (West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents.
abstract: BACKGROUND
  Endophytic fungi, being a prolific source of bioactive secondary metabolites, are of great interest for natural product discovery.
  
  
  OBJECTIVE
  Isolation and partial characterization of endophytic fungi inhabiting the leaves and woody parts of Taxus fuana Nan Li & R.R. Mill. (Taxaceae) and evaluation of biological activity.
  
  
  METHODS
  Endophytic fungal isolates were identified by molecular analysis of internal transcribed spacer (ITS) regions of 18S rDNA. Extracts of the endophytic fungi cultured on potato dextrose agar and modified medium were evaluated using cancer chemoprevention bioassays [inhibition of TNF-α-induced NFκB, aromatase and inducible nitric oxide synthase (iNOS); induction of quinone reductase 1 (QR1)] and growth inhibition with MCF-7 cells.
  
  
  RESULTS
  Nine of 15 fungal isolates were identified as belonging to Epicoccum, Mucor, Penicillium, Chaetomium, Paraconiothriym, Plectania or Trichoderma. Five of the 15 extracts inhibited NFκB activity (IC50values ranging between 0.18 and 17 μg/mL) and five inhibited iNOS (IC50values ranging between 0.32 and 12.9 μg/mL). In the aromatase assay, only two isolates mediated inhibition (IC50values 12.2 and 10.5 μg/mL). With QR1 induction, three extracts exhibited significant activity (concentrations to double activity values ranging between 0.20 and 5.5 μg/mL), and five extracts inhibited the growth of MCF-7 cells (IC50values ranging from 0.56 to 17.5 μg/mL). Six active cultures were derived from woody parts of the plant material.
  
  
  CONCLUSIONS
  The endophytic fungi studied are capable of producing pharmacologically active natural compounds. In particular, isolates derived from the wood of Taxus fuana should be prioritized for the isolation and characterization of bioactive constituents.
authors.affiliation: a Department of Biotechnology , Quaid-i-Azam University , Islamabad , Pakistan.|b Department of Microbiology , Quaid-i-Azam University , Islamabad , Pakistan.|c Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy , University of Hawaii at Hilo , Hilo , HI , USA.
authors.forename: Nighat
authors.initials: N
authors.lastname: Fatima
authors.affiliation: c Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy , University of Hawaii at Hilo , Hilo , HI , USA.
authors.forename: Tamara P
authors.initials: TP
authors.lastname: Kondratyuk
authors.affiliation: c Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy , University of Hawaii at Hilo , Hilo , HI , USA.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: c Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy , University of Hawaii at Hilo , Hilo , HI , USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Marler
authors.affiliation: b Department of Microbiology , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Muniba
authors.initials: M
authors.lastname: Jadoon
authors.affiliation: b Department of Microbiology , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Muneer Ahmed
authors.initials: MA
authors.lastname: Qazi
authors.affiliation: b Department of Microbiology , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Hira
authors.initials: H
authors.lastname: Mehboob Mirza
authors.affiliation: b Department of Microbiology , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Ibrar
authors.initials: I
authors.lastname: Khan
authors.affiliation: b Department of Microbiology , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Naima
authors.initials: N
authors.lastname: Atiq
authors.affiliation: c Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy , University of Hawaii at Hilo , Hilo , HI , USA.
authors.forename: Leng Chee
authors.initials: LC
authors.lastname: Chang
authors.affiliation: b Department of Microbiology , Quaid-i-Azam University , Islamabad , Pakistan.
authors.forename: Safia
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: c Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy , University of Hawaii at Hilo , Hilo , HI , USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
mesh_terms: D016588:Anticarcinogenic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D047072:Aromatase Inhibitors / Q000494:pharmacology; D060026:Endophytes / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D020946:Taxus / Q000382:microbiology*
chemical_list: D016588:Anticarcinogenic Agents; D047072:Aromatase Inhibitors; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human
keywords: Aromatase; NFκB; endophytes; growth inhibition; iNOS; phylogenetics; quinone reductase