YD277 suppresses triple-negative breast cancer partially through activating the endoplasmic reticulum stress pathway

Zekun Chen, Qiuju Wu, Ye Ding, Wenhui Zhou, Rong Liu, Haiying Chen, Jia Zhou, Jing Feng, Ceshi Chen

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Triple-negative breast cancer (TNBC) is an aggressive malignancy with poor clinical outcomes. YD277 is a novel small molecule derived from ML264, a KLF5 inhibitor that elicits cytotoxic effects in colon cancer cell lines. Our previous studies suggest that Krüpple-like factor 5 (KLF5) is a promising therapeutic target for TNBC. In this study, we demonstrated that YD277 significantly induced G1 cell cycle arrest and apoptosis in MDA-MB-231 and MDA-MB-468 TNBC cells, independent of KLF5 inhibition. YD277 also reduced the protein expression levels of Cyclin D1, Bcl2 and Bclxl and promoted the expression of p21 and p27. Moreover, the pro-apoptotic activity of YD277 in TNBC was mediated by the transcription of IRE1α, a key molecule in the endoplasmic reticulum (ER) stress pathway. Finally, YD277 (15 mg/kg) significantly suppressed the growth of MDA-MB-231 tumor xenografts in nude mice. These findings indicate that YD277 is a promising chemotherapeutic candidate for TNBC.

Original languageEnglish (US)
Pages (from-to)2339-2349
Number of pages11
JournalTheranostics
Volume7
Issue number8
DOIs
StatePublished - 2017

Keywords

  • ER stress
  • IRE1α
  • KLF5
  • Triple-Negative Breast Cancer
  • YD277

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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