Effects of CDDO‑TFEA on non‑small cell lung cancer growth, apoptosis, and stemness via the MEK/ERK pathway.

Authors

Jui-Ying Lee, Chia-Li Chung, Tzu-Ting Tseng, Shih-Hsun Kuo, Yu-Peng Liu, Ming-Tsang Wu, Hung-Pei Tsai, Aij-Lie Kwan

Published in

Journal of cancer research and clinical oncology. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, and therapeutic resistance limits durable responses. We investigated the antitumor activity of CDDO-TFEA, a synthetic trifluoroethyl amide derivative of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, in NSCLC models.
A549 and H1299 cells were treated with CDDO-TFEA and evaluated using MTT assays, Annexin V/7-aminoactinomycin D flow cytometry, tumorsphere and tube-formation assays, immunoblotting, and A549 xenograft experiments.
CDDO-TFEA decreased cell viability in a dose-dependent manner and induced apoptosis, as indicated by increased Annexin V positivity, PARP cleavage, cleaved caspase-3 expression, and TUNEL positivity. At 200 nM, CDDO-TFEA significantly suppressed tumorsphere formation in both cell lines and reduced CD133, octamer-binding transcription factor 4, SRY-box transcription factor 2, and vascular endothelial growth factor expression. Because only A549 cells formed tube-like networks, angiogenesis-related phenotypes were evaluated in A549 cells and were markedly inhibited by CDDO-TFEA. Mechanistically, CDDO-TFEA increased extracellular signal-regulated kinase phosphorylation, whereas MEK inhibition by U0126 or trametinib partially attenuated CDDO-TFEA-induced apoptosis and the suppression of tumorsphere formation, tube-like network formation, and stemness- and angiogenesis-related marker expression. In vivo, systemic CDDO-TFEA administration dose-dependently inhibited xenograft tumor growth.
CDDO-TFEA exerts antitumor activity in NSCLC by inducing apoptosis and suppressing stemness-associated and angiogenesis-related phenotypes, partly through mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling. These findings support further preclinical development of CDDO-TFEA in NSCLC.

PMID:
42455368
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.