Rosemary Extract Inhibits Proliferation, Survival, Akt, and mTOR Signaling in Triple-Negative Breast Cancer Cells

Int J Mol Sci. 2020 Jan 27;21(3):810. doi: 10.3390/ijms21030810.

Abstract

Breast cancer is the most commonly diagnosed cancer in women. Triple-negative (TN) breast cancer lacks expression of estrogen receptor (ER), progesterone receptor (PR) as well as the expression and/or gene amplification of human epidermal growth factor receptor 2 (HER2). TN breast cancer is aggressive and does not respond to hormone therapy, therefore new treatments are urgently needed. Plant-derived chemicals have contributed to the establishment of chemotherapy agents. In previous studies, rosemary extract (RE) has been found to reduce cell proliferation and increase apoptosis in some cancer cell lines. However, there are very few studies examining the effects of RE in TN breast cancer. In the present study, we examined the effects of RE on TN MDA-MB-231 breast cancer cell proliferation, survival/apoptosis, Akt, and mTOR signaling. RE inhibited MDA-MB-231 cell proliferation and survival in a dose-dependent manner. Furthermore, RE inhibited the phosphorylation/activation of Akt and mTOR and enhanced the cleavage of PARP, a marker of apoptosis. Our findings indicate that RE has potent anticancer properties against TN breast cancer and modulates key signaling molecules involved in cell proliferation and survival.

Keywords: apoptosis; breast cancer; proliferation; rosemary extract; signaling; survival.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rosmarinus / chemistry*
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*
  • Triple Negative Breast Neoplasms / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases