Pramanik, Arindam, Wang, Dapeng, Kobza, Dagmara, Reed, Lewis P, Beales, Paul A and Hughes, Thomas ORCID: https://orcid.org/0000-0003-1169-3386 (2026) Phospholipase A2 enhances the cytotoxic activity of membranolytic peptide Polybia MP1 in some breast epithelial cells. Biochemistry and Biophysics Reports. (In Press)

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Abstract

MP1, a peptide from the venom of the wasp Polybia paulista, has been investigated for anti-microbial and anti-cancer properties. The peptide binds and disrupts external-facing lipid membranes of various cell types, thereby reducing cellular viability, with some reported selectivity for cancer cells. The molecular basis of selectivity is poorly understood. We have assessed MP1 activity in a panel of human cells, with the aims of establishing the types most suited to development of future MP1-derived therapies and identifying molecular factors influencing responses.

Cellular viability was tested in 64 cancer cell lines after treatment with MP1 to determine IC50 values. These varied by 8.5-fold across the panel, with blood cancer lines proving most sensitive and colorectal cancer lines most resistant, and breast cells showing the greatest variance. Transcriptome data were downloaded for cell lines and relationships between expression levels of each individual gene and IC50 values were assessed using linear regression. 67 genes demonstrated significant correlations after correction for multiple testing, within which lipases were significantly over-represented. The impact on viability of exogenous phospholipase A2 with and without MP1 was tested in four different breast epithelial cell lines that represented a wide range of intrinsic sensitivities to MP1 alone. Phospholipase A2 had little significant influence on viability alone, but caused potent and dose-dependent potentiation of MP1-induced cytotoxicity in two of the four cell lines tested.

We conclude that phospholipase A2 and MP1 act together on some breast cancer cell membranes, and that this combinatorial influence could impact on future development of MP1 as a cancer therapy.

Item Type:	Article
Status:	In Press
Subjects:	Q Science > Q Science (General)
School/Department:	School of Health Sciences
URI:	https://ray.yorksj.ac.uk/id/eprint/15858

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