Oncotarget

Research Papers:

α-Tocopherol succinate enhances pterostilbene anti-tumor activity in human breast cancer cells in vivo and in vitro

Ka-Wai Tam, Chi-Tang Ho, Shih-Hsin Tu, Wen-Jui Lee, Ching-Shui Huang, Ching-Shyang Chen, Chih-Hsiung Wu, Chia-Hwa Lee _ and Yuan-Soon Ho

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Oncotarget. 2018; 9:4593-4606. https://doi.org/10.18632/oncotarget.23390

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Abstract

Ka-Wai Tam1,2,3, Chi-Tang Ho4, Shih-Hsin Tu3,5,6,7, Wen-Jui Lee8, Ching-Shui Huang3,9, Ching-Shyang Chen3,10,11, Chih-Hsiung Wu2,3,7,12, Chia-Hwa Lee7,13,14,15,* and Yuan-Soon Ho7,14,15,16,17,*

1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

2Department of Surgery, Division of General Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan

3Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

4Department of Food Science, Rutgers University, New Brunswick, NJ, USA

5Breast Medical Center, Taipei Medical University Hospital, Taipei, Taiwan

6Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan

7Comprehensive Cancer Center of Taipei Medical University, Taipei, Taiwan

8Department of Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

9Department of Surgery, Division of Breast Surgery, Cathay General Hospital, Taipei, Taiwan

10Comprehensive Breast Health Center, Taipei Medical University Hospital, Taipei, Taiwan

11Department of Surgery, Mennonite Christian Hospital, Hualien, Taiwan

12Department of Surgery, En Chu Kong Hospital, New Taipei City, Taiwan

13Department of Laboratory Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan

14 School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

15Ph.D. Program in Medicine Biotechnology, College of Medicine, Taipei Medical University, Taipei, Taiwan

16Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan

17Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

*These authors contributed equally to this work

Correspondence to:

Chia-Hwa Lee, email: chlee@tmu.edu.tw

Yuan-Soon Ho, email: yuansn@tmu.edu.tw

Keywords: vitamin E; tocopherol-associated protein; α-tocopheryl succinate; pterostilbene; breast cancer

Received: October 05, 2017     Accepted: December 05, 2017     Published: December 17, 2017

ABSTRACT

Vitamin E (Vit. E) is considered an essential dietary nutrient for humans and animals. An enormous body of evidence indicates the biological and protective effects of Vit. E consumption. Tocopherol-associated protein (TAP) is a major tocopherol-binding protein affecting Vit. E stimulation and downstream signaling transduction. However, how Vit. E utilizes TAP as an anti-cancer mechanism remains unclear.Microarray analysis of signature gene profiles in breast cancer cells treated with α-tocopheryl succinate (α-TOS, a Vit. E isoform) resulted in cell cycle arrest and anti-cancer activity in breast cancer cells. Pterostilbene (PS), a natural dietary antioxidant found in blueberries, in combination with α-TOS synergistically maximized breast cancer cell growth inhibition by disrupting signal transduction, transcription factors and cell cycle proteins. In a xenograft mouse model, PS treatment with Vit. E inhibited breast tumor growth and cell invasion, which were evaluated using our recently developed circulating tumor cell (CTC) detection assay. Because dietary Vit. E and PS supplementation contributed to preventative and therapeutic effects in vitro and in vivo, this combination may benefit breast cancer therapy in the clinic.


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