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Tocopherols inhibit estrogen-induced cancer stemness and OCT4 signaling in breast cancer

Min Ji Bak1, Philip Furmanski1, Naing Lin Shan1

  • 1Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.

Carcinogenesis
|May 31, 2018
PubMed

Insights

Tocopherols can inhibit estrogen-driven breast cancer stemness and invasion by reducing key stem cell markers. This suggests tocopherols may be a potential therapeutic strategy against estrogen-sensitive breast cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Estrogen is implicated in breast cancer development, potentially by enhancing tumor stem cell properties.
  • Tocopherols (Vitamin E) are known to inhibit breast cancer progression.
  • The precise mechanisms by which estrogen influences breast cancer stemness and how tocopherols counteract these effects require further investigation.

Purpose of the Study:

  • To investigate the effects of tocopherols on estrogen-mediated regulation of breast cancer stemness.
  • To elucidate the molecular mechanisms underlying tocopherol's action in estrogen-stimulated breast cancer stem cells.

Main Methods:

  • Utilized the MCF-7 tumorsphere culture system to enrich for breast cancer stem cells.
  • Assessed the impact of estrogen and tocopherol treatments on stem cell markers (CD44, OCT4, SOX-2), aldehyde dehydrogenase activity, and tumorsphere formation.
  • Investigated the role of OCT4 in cell invasion and the inhibitory effects of tocopherols on OCT4-mediated invasion.

Main Results:

  • Estrogen treatment increased breast cancer stem cell populations (CD44+/CD24-, aldehyde dehydrogenase activity) and tumorsphere growth.
  • Tocopherols effectively inhibited estrogen-induced expansion of the stem cell population.
  • Tocopherols decreased levels of stem cell markers (OCT4, CD44, SOX-2) and estrogen-responsive genes (TFF/pS2, cathepsin D, progesterone receptor, SERPINA1).
  • Overexpression of OCT4 promoted cell invasion, and tocopherols counteracted these OCT4-driven invasive effects.

Conclusions:

  • Tocopherols demonstrate a potential inhibitory effect on estrogen-induced stemness and cell invasion in breast cancer.
  • Tocopherols may offer a therapeutic avenue by targeting the interplay between estrogen, stemness, and invasiveness in breast cancer.

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