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Scientific Reports

Scientific Reports

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Tenovin 3 induces apoptosis and ferroptosis in EGFR 19del non small cell lung cancer cells

Published:1 April 2024 DOI: 10.1038/s41598-024-58499-5 PMID: 38561419
Sha Lv,?Qianrong Pan,?Weijin Lu,?Weisong Zhang,?Naike Wang,?Lijuan Huang,?Lianjing Li,?Jieyao Liu,?Jiamei Ma,?Zhan Li,?Yong Huang,?Qiudi Deng,?Xueping Lei

Abstract

Epidermal growth factor receptor (EGFR) exon 19 deletion is a major driver for the drug resistance of non-small cell lung cancer (NSCLC). Identification small inhibitor capable of selectively inhibiting EGFR-19del NSCLC is a desirable strategy to overcome drug resistance in NSCLC. This study aims to screen an inhibitor for EGFR exon 19 deletion cells and explore its underlying mechanism. High through-put screen was conducted to identify an inhibitor for EGFR-19del NSCLC cells. And tenovin-3 was identified as a selective inhibitor of PC9 cells, an EGFR-19del NSCLC cells. Tenovin-3 showed particular inhibition effect on PC9 cells proliferation through inducing apoptosis and ferroptosis. Mechanistically, tenovin-3 might induce the apoptosis and ferroptosis of PC9 cells through mitochondrial pathway, as indicated by the change of VDAC1 and cytochrome c (cyt c). And bioinformatics analyses showed that the expression levels of SLC7A11 and CPX4 were correlated with NSCLC patient's survival. Our findings provide evidences for tenovin-3 to be developed into a novel candidate agent for NSCLC with EGFR exon 19 deletion. Our study also suggests that inducing ferroptosis may be a therapeutic strategy for NSCLC with EGFR exon 19 deletion.

Substances (24)

Materials
Procduct Name CAS Molecular Formula Supplier Price
AZD-9291 1421373-65-0 C28H33N7O2 429 suppliers $4.00-$1800.00
AZD-9291 1421373-65-0 C28H33N7O2 429 suppliers $4.00-$1800.00
AZD-9291 1421373-65-0 C28H33N7O2 429 suppliers $4.00-$1800.00
AZD-9291 1421373-65-0 C28H33N7O2 429 suppliers $4.00-$1800.00
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 247 suppliers $10.00-$2822.00
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 247 suppliers $10.00-$2822.00
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 247 suppliers $10.00-$2822.00
Ferrostatin-1 (Fer-1) 347174-05-4 C15H22N2O2 247 suppliers $10.00-$2822.00
RSL3 1219810-16-8 C23H21ClN2O5 218 suppliers $13.00-$1872.00
RSL3 1219810-16-8 C23H21ClN2O5 218 suppliers $13.00-$1872.00

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