St. John's Wort Suppresses Growth in Triple-Negative Breast Cancer Cell Line MDA-MB-231 by Inducing Prodeath Autophagy and Apoptosis

Nutrients. 2020 Oct 17;12(10):3175. doi: 10.3390/nu12103175.

Abstract

The rational regulation of programmed cell death by means of autophagy and apoptosis has been considered a potential treatment strategy for cancer. We demonstrated the inhibitory effect of St. John's Wort (SJW) on growth in the triple-negative breast cancer (TNBC) cell line and xenografted mice and its target mechanism concerning autophagic and apoptotic cell death. SJW ethanol extract (SJWE) inhibited proliferation in a dose-dependent manner. SJWE treatment dramatically increased autophagy flux and apoptosis compared with the control. The autophagy inhibitor, 3-methyladenine (3-MA), reversed the SJWE-induced inhibition of cell proliferation and regulation of autophagy and apoptosis, indicating that SJWE induced apoptosis through prodeath autophagy. Furthermore, SJWE inhibited tumor growth and induced autophagy and apoptosis in the tumor of MDA-MB-231 xenografted athymic nude mice. Our results indicate that SJWE might have great potential as a new anticancer therapy for triple-negative breast cancer by inducing prodeath autophagy and apoptosis.

Keywords: St. John’s Wort; apoptosis; autophagy; triple-negative breast cancer.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Animals
  • Antineoplastic Agents, Phytogenic*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Dose-Response Relationship, Drug
  • Hypericum / chemistry*
  • Mice, Nude
  • Neoplasm Transplantation
  • Phytotherapy*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • 3-methyladenine
  • Adenine