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European Journal of Nutrition

, Volume 54, Issue 2, pp 265–272 | Cite as

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

  • Anh Thu Tran
  • Malathi Ramalinga
  • Habib Kedir
  • Robert Clarke
  • Deepak KumarEmail author
Original Contribution

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.

Keywords

Vitamin E Tocomin® Tocotrienols Breast cancer Apoptosis Autophagy 

Abbreviations

T3s

Tocotrienols

Ts

Tocopherols

3-MA

3-Methyladenine

ER

Estrogen receptor

TRF

Tocotrienol-rich fraction of palm oil

γ-T3

Gamma tocotrienol

ER stress

Endoplasmic reticulum stress

UPR

Unfolded protein response

MDC

Monodansylcadaverine

PI3K

Phosphoinositide 3-kinase

mTOR

Mammalian Target of Rapamycin

LC3β

Microtubule-associated protein 1 light chain 3 beta

Notes

Acknowledgments

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.

Conflict of interest

The authors have no potential conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Anh Thu Tran
    • 1
  • Malathi Ramalinga
    • 1
  • Habib Kedir
    • 1
  • Robert Clarke
    • 2
  • Deepak Kumar
    • 1
    • 2
    Email author
  1. 1.Cancer Research Laboratory, Department of Biology and ChemistryUniversity of the District of ColumbiaWashingtonUSA
  2. 2.Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonUSA

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