Epidermal growth factor potentiates EGFR(Y992/1173)-mediated therapeutic response of triple negative breast cancer cells to cold atmospheric plasma-activated medium

Peiyu Wang, Renwu Zhou, Rusen Zhou, Shuo Feng, Liqian Zhao, Wenshao Li, Jinyong Lin, Aleksandra Rajapakse, Chia Hwa Lee, Frank B. Furnari, Antony W. Burgess, Jennifer H. Gunter, Gang Liu, Kostya (Ken) Ostrikov, Derek J. Richard, Fiona Simpson, Xiaofeng Dai, Erik W. Thompson

Research output: Contribution to journalArticlepeer-review

Abstract

Cold atmospheric plasma (CAP) holds promise as a cancer-specific treatment that selectively kills various types of malignant cells. We used CAP-activated media (PAM) to  utilize a range of the generated short- and long-lived reactive species. Specific antibodies, small molecule inhibitors and CRISPR/Cas9 gene-editing approaches showed an essential role for receptor tyrosine kinases, especially epidermal growth factor (EGF) receptor, in mediating triple negative breast cancer (TNBC) cell responses to PAM. EGF also dramatically enhanced the sensitivity and specificity of PAM against TNBC cells. Site-specific phospho-EGFR analysis, signal transduction inhibitors and reconstitution of EGFR-depleted cells with EGFR-mutants confirmed the role of phospho-tyrosines 992/1173 and phospholipase C gamma signaling in up-regulating levels of reactive oxygen species above the apoptotic threshold. EGF-triggered EGFR activation enhanced the sensitivity and selectivity of PAM effects on TNBC cells. The proposed approach based on the synergy of CAP and EGFR-targeted therapy may provide new opportunities to improve the clinical management of TNBC.

Original languageEnglish
Article number102976
JournalRedox Biology
Volume69
DOIs
Publication statusPublished - Feb 2024

Keywords

  • Apoptosis
  • Cold atmospheric plasma
  • Epithelial growth factor receptor
  • Triple negative breast cancer

ASJC Scopus subject areas

  • Organic Chemistry

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