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Article

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

  • Authors:
    • Taolan Zhang
    • Weijuan Zhang
    • Meng Hao
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    Affiliations: Department of Pharmacy, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan 421001, P.R. China, Department of Executive Management, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
  • Pages: 337-348
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    Published online on: November 19, 2020
       https://doi.org/10.3892/or.2020.7860
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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