The antipsychotic chlorpromazine suppresses YAP signaling, stemness properties, and drug resistance in breast cancer cells

Chang En Yang, Wen Ying Lee, Hung Wei Cheng, Chu Hung Chung, Fu Lowng Mi, Cheng Wei Lin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The major obstacle in current cancer therapy is the existence of cancer stem cells (CSCs), which are responsible for therapeutic resistance and contribute to metastasis and recurrence. Identification of reliable biomarkers for diagnostic and therapeutic targets is necessary for drug development and cancer treatment. In this study, we identified that the antipsychotic chlorpromazine (CPZ) exhibited potent anti-breast cancer and anti-CSC capabilities. Treatment with CPZ suppressed stemness properties including mammosphere formation, aldehyde dehydrogenase (ALDH) activity, and stemness-related gene expressions in breast cancer cells and CSCs. Moreover, CPZ increased the susceptibility of breast cancer MCF7 cells and drug-resistant MCF7/ADR cells when combined with chemotherapies. Mechanistically, we identified that CPZ suppressed yes-associated protein (YAP) through modulating Hippo signaling and promoting proteasomal degradation of YAP. Elevated expression of YAP was confirmed to be crucial for stemness-related gene expressions, and was associated with invasiveness and stem-like signatures in breast cancer patients. Moreover, overexpression of YAP conferred poor outcomes particularly of basal-like breast cancer patients. Our data showed that YAP is a promising therapeutic target for breast CSCs, and CPZ has the potential to be a repurposed drug for breast cancer treatment.

Original languageEnglish
Pages (from-to)28-35
Number of pages8
JournalChemico-Biological Interactions
Volume302
DOIs
Publication statusPublished - Apr 1 2019

Keywords

  • Antipsychotic
  • Breast cancer
  • Cancer stem cells
  • YAP

ASJC Scopus subject areas

  • Toxicology

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