Autophagy inhibitor 3-methyladenine potentiates apoptosis induced by dietary tocotrienols in breast cancer cells

Anh Thu Tran, Malathi Ramalinga, Habib Kedir, Robert Clarke, Deepak Kumar

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Introduction: Tocomin® represents commercially available mixture of naturally occurring tocotrienols (T3s) and tocopherols extracted from palm oil/palm fruits that possess powerful antioxidant, anticancer, neuro/cardioprotective and cholesterol-lowering properties. Cellular autophagy represents a defense mechanism against oxidative stress and several anticancer compounds. Recently, we reported that T3s induce apoptosis and endoplasmic reticulum stress in breast cancer cells. Methodology: We studied the effects of Tocomin® on MCF-7 and MDA-MB 231 breast cancer cells and non-tumor MCF-10A cells. Results: Tocomin® inhibited cell proliferation and induced apoptosis in both MCF-7 and MDA-MB 231 breast cancer cell lines without affecting the viability of MCF-10A cells. We also showed that Tocomin® negatively modulates phosphoinositide 3-kinase and mTOR pathways and induces cytoprotective autophagic response in triple negative MDA-MB 231 cells. Lastly, we demonstrate that autophagy inhibitor 3-methyladenine (3-MA) potentiated the apoptosis induced by Tocomin® in MDA-MB 231 cells. Conclusion: Together, our data indicate anticancer effects of Tocomin® in breast cancer cells, which is potentiated by the autophagy inhibitor 3-MA.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalEuropean Journal of Nutrition
Volume54
Issue number2
DOIs
StatePublished - Mar 2015
Externally publishedYes

Bibliographical note

Funding Information:
We thank Carotech for the gift of Tocomin. HK is an MARC U*STAR Honors Fellow (GM087172). We thank Dr. Anvesha Srivastava for assisting with submission of the manuscript. DK is funded by CA141935, CA162264 from the National Cancer Institute. ®

Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.

Keywords

  • Apoptosis
  • Autophagy
  • Breast cancer
  • Tocomin
  • Tocotrienols
  • Vitamin E

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