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Identification of ergosterol peroxide in the endophytic fungus Pestalotiopsis microspora and evaluation of its efficacy in overcoming cancer drug resistance

Rajender Goud Arolla, Pavan Kumar Pallerla, Neeraja Cherukupalli, Rama Krishna Kancha, Prabhakar Sripadi, Akella V. S. Sarma, Venkateswara Rao Khareedu & Dashavantha Reddy Vudem

Sydowia 74: 327-334

Published online on January 21st, 2022

Arolla R.G., Pallerla P.K., Cherukupalli N., Kancha R.K., Sripadi P., Sarma A.V.S., Khareedu V.R. & Vudem D.R. (2022) Identification of ergosterol peroxide in the endophytic fungus Pestalotiopsis microspora and evaluation of its efficacy in overcoming cancer drug resistance. – Sydowia 74: 327–334. Endophytic fungi are a good source of bioactive compounds. A fungal endophyte was isolated from stem sections of Garcinia lanceifolia and identified as Pestalotiopsis microspora based on morphological characteristics and nucleotide sequence of ITS1- 5.8S-ITS2 template region for r-RNA. A compound from the in vitro cultured fungal-biomass was purified and identified it as Ergosterol Peroxide (EP) based on 1H NMR, 13C NMR, 1H -13C HSQC, 1H -1H DQFCOSY, DEPT-135 and HR-ESI-MS spectra. EP exhibited cytotoxic activity against adherent tumor cell lines HeLa, MCF7, BT474 and A549 with IC50 values of 12.72±0.21, 14.78±0.22, 16±0.15 and 18.23±0.40 µg/ml, respectively as well as a suspension cell line K562 (IC50 16.05±1.11 µg/ml). EP also proved potent against drug resistant cell lines, K562-IR2 and K562-IR1 with IC50 values 9.42±0.12 and 12.69±0.23 µg/ml, respectively. EP treatment showed dose-dependent reduction in phosphorylation of pro-survival STAT5 protein both in wild type and imatinib-resistant cell lines. An endophytic fungus, P. microspora, isolated in the present study can serve as a good source of bioactive molecule EP. For the first time, this study demonstrated potent cytotoxic activity of EP against imatinib resistant cell lines K562-IR1 and K562-IR2. EP can serve as a promising drug lead molecule for overcoming cancer drug-resistance.

Keywords: endophytic fungus, ergosterol peroxide, anti-cancer activity, drug resistance.

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