Cytotoxic activity of crude extracts from Datura stramonium's fungal endophytes against A549 lung carcinoma and UMG87 glioblastoma cell lines and LC-QTOF-MS/MS based metabolite profiling

BMC Complement Altern Med. 2019 Nov 21;19(1):330. doi: 10.1186/s12906-019-2752-9.

Abstract

Background: Endophytic fungi are a proven source of bioactive secondary metabolites that may provide lead compounds for novel drug discovery. In this study, crude extracts from fungal endophytes isolated from Datura stramonium were evaluated for cytotoxic activity on two human cancer cell lines.

Methods: Fungal endophytes were isolated from surface sterilized aerial parts of D. stramonium and identified using molecular, morphological and phylogenetic methods. Ethyl acetate crude extracts from these isolates were evaluated for cytotoxic activity on A549 lung carcinoma and UMG87 glioblastoma cell lines. Metabolite profiling was then performed by liquid chromatography coupled to quadrupole time-of-flight with tandem mass spectrometry (LC-QTOF-MS/MS) for the cytotoxic crude extract.

Results: Eleven fungal endophytes were identified from D. stramonium. Significant cytotoxicity was only observed from the crude extract of Alternaria sp. KTDL7 on UMG87 glioblastoma cells (IC50 = 21.49 μg/ml). Metabolite profiling of this crude extract tentatively revealed the presence of the following secondary metabolites: 1,8-dihydroxynaphthalene (1), anserinone B (2), phelligridin B (3), metacytofilin (4), phomopsidin (5) and vermixocin A (6). Compounds 2 and 3 have been shown to be cytotoxic in literature.

Conclusion: The findings in this study suggest that the crude extract of Alternaria sp. KTDL7 possesses compound(s) cytotoxic to glioblastoma multiforme cells. Future studies to isolate and characterize the cytotoxic compound(s) from this fungus could result in lead development of a fungal-based drug for glioblastoma multiforme treatment.

Keywords: Cytotoxicity; Datura stramonium; Endophytes; Glioblastoma; Lung carcinoma; Secondary metabolites.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • Chromatography, Liquid
  • Datura stramonium / microbiology*
  • Endophytes / chemistry
  • Endophytes / genetics
  • Endophytes / metabolism
  • Fungi / chemistry
  • Fungi / genetics
  • Fungi / metabolism
  • Humans
  • Tandem Mass Spectrometry

Substances

  • Antineoplastic Agents
  • Biological Products