In: Sydowia 74, (2022): 327-342; ISSN 0082-0598, DOI 10.12905/0380.sydowia74-2021-0327, Published online on January 21, 2022

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 Cherukupalli1, Rama Krishna Kancha,
Prabhakar Sripadi, Akella V. S. Sarma, Venkateswara Rao Khareedu & Dashavantha Reddy Vudem,*

Centre for Plant Molecular Biology, Osmania University, Hyderabad, 500 007, India
Molecular Medicine and Therapeutics Laboratory, CPMB, Osmania University, Hyderabad, 500 007, India
Department of Analytical & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India
Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh-201002, India
Centre for Mass Spectrometry, Department of Analytical & Structural Chemistry, CSIR-Indian Institute of Chemical
Technology, Hyderabad, 500 007, India

* e-mail: vdreddycpmb@gmail.com

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.

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