Phenethyl isothiocyanate reduces breast cancer stem cell-like properties by epigenetic reactivation of CDH1

  • Authors:
    • Taolan Zhang
    • Weijuan Zhang
    • Meng Hao
  • View Affiliations

  • Published online on: November 19, 2020     https://doi.org/10.3892/or.2020.7860
  • Pages: 337-348
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Abstract

Breast cancer is the most frequently diagnosed malignancy and leading cause of cancer-related deaths among women worldwide. Tumor recurrence, or metastasis, is caused by cancer stem cells and has a dismal prognosis for breast cancer patients. Thus, targeting breast cancer stem cells (BCSCs) for eradication is a potential method to improve clinical outcomes. Phenethyl isothiocyanate (PEITC) is a novel epigenetic regulator derived from cruciferous vegetables that has marked antitumor effects. However, the exact mechanism of these antitumor effects by PEITC is unknown. As breast cancer progresses, a tumor suppressor in the breast, cadherin 1 (CDH1), is silenced by hypermethylation of the promoter region, further promoting the stem cell-like properties of cancer. Herein, the ability of PEITC to reduce BCSC-like properties by epigenetic reactivation of CDH1 was investigated by multiple analyses such as MTT, colony formation and sphere formation assays, methylation-specific PCR, western blot analysis, Co-IP and qPCR. It was revealed that PEITC inhibited colony and mammosphere formation and decreased the expression of protein markers associated with BCSC-like properties via epigenetic reactivation of CDH1. Further exploration of this mechanism revealed inhibitory effects of PEITC on DNMTs and HDACs, which play a pivotal role in demethylating the hypermethylated CDH1 promoter region. Reactivated CDH1 suppressed the Wnt/β-catenin pathway which confers BCSC-properties in breast cancer cells. These findings suggest a novel method to eradicate BCSCs from breast cancer patients.

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January-2021
Volume 45 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang T, Zhang W and Hao M: Phenethyl isothiocyanate reduces breast cancer stem cell-like properties by epigenetic reactivation of CDH1. Oncol Rep 45: 337-348, 2021
APA
Zhang, T., Zhang, W., & Hao, M. (2021). Phenethyl isothiocyanate reduces breast cancer stem cell-like properties by epigenetic reactivation of CDH1. Oncology Reports, 45, 337-348. https://doi.org/10.3892/or.2020.7860
MLA
Zhang, T., Zhang, W., Hao, M."Phenethyl isothiocyanate reduces breast cancer stem cell-like properties by epigenetic reactivation of CDH1". Oncology Reports 45.1 (2021): 337-348.
Chicago
Zhang, T., Zhang, W., Hao, M."Phenethyl isothiocyanate reduces breast cancer stem cell-like properties by epigenetic reactivation of CDH1". Oncology Reports 45, no. 1 (2021): 337-348. https://doi.org/10.3892/or.2020.7860