Trichothecin from Endophytic Fungus Trichothecium sp. and its Anticancer Effect on Murine Melanoma and Breast Cancer Cell Lines
Ravindra Taware, Prasad Abnave, Deepak Patil, Pattuparambil Ramanpillai Rajamohananan, Remya Raja, Gowrishankar Soundararajan, Gopal Chandra Kundu, Mahesh Kumar Dhondhiram Kharat, Kalpana Pai and Absar Ahmad
Affiliation: Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune - 411008, India.
Endophytic fungi were isolated from the leaves of medicinal herb Phyllanthus sp. sourced
from different areas of Pune and then screened for Trichothecin production. Out of 30 endophytic fungal
cultures isolated and screened, only one AAP-PS-1 was found to produce Trichothecin extracellularly
in appreciable amounts and was identified as Trichothecium sp. by morphological, cultural and
molecular methods. Trichothecin, a sesquiterpene from endophytic fungus Trichothecium sp. was purified
using prep TLC, RP-HPLC; quantified and completely characterised by UV-VIS, FTIR, ESI-MS, HRMS and 1D and
2D NMR techniques. One liter of Trichothecium sp. yielded 4.25 mg of Trichothecin. We screened Trichothecin for antifungal
activity against filamentous fungi and yeast, apoptotic activity against B16F10 cells, anticancer activity against
MDA-MB-231, HeLa and B16F10 cells as well as antimetastatic activity against MDA-MB-231 cell line. It was observed
that Trichothecin inhibited MDA-MB-231 cell migration and arrested B16F10 cells at G2/M phase indicating its potential
as antimetastatic and antiproliferative compound. Further, for selectivity, we checked for its cytotoxicity against mouse
embryonic fibroblast (NIH3T3) and human peripheral blood mononuclear cells (PBMC) and found that it was not cytotoxic
in the given concentration range of Tricothecin used against cancer cell lines. Assessment of toxicity towards human
RBC revealed only less than 0.1% hemolysis as compared to Triton X-100 suggesting safe nature of Trichothecin. It was
also found that Trichothecin exhibits anti-fungal activity against a range of filamentous fungi and yeast. Given its potent
and selective anticancer activity, Trichothecin could be used as scaffold for chemical and biological transformations to
generate analogues with better pharmacological properties.
Keywords: Endophytic fungi, Trichothecium sp., Phyllanthus sp., trichothecin, anti-proliferation, cancer cell migration.
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