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

// Ka-Wai Tam 1, 2, 3 , Chi-Tang Ho 4 , Shih-Hsin Tu 3, 5, 6, 7 , Wen-Jui Lee 8 , Ching-Shui Huang 3, 9 , Ching-Shyang Chen 3, 10, 11 , Chih-Hsiung Wu 2, 3, 7, 12 , Chia-Hwa Lee 7, 13, 14, 15, * and Yuan-Soon Ho 7, 14, 15, 16, 17, * 1 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 2 Department of Surgery, Division of General Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan 3 Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 4 Department of Food Science, Rutgers University, New Brunswick, NJ, USA 5 Breast Medical Center, Taipei Medical University Hospital, Taipei, Taiwan 6 Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan 7 Comprehensive Cancer Center of Taipei Medical University, Taipei, Taiwan 8 Department of Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 9 Department of Surgery, Division of Breast Surgery, Cathay General Hospital, Taipei, Taiwan 10 Comprehensive Breast Health Center, Taipei Medical University Hospital, Taipei, Taiwan 11 Department of Surgery, Mennonite Christian Hospital, Hualien, Taiwan 12 Department of Surgery, En Chu Kong Hospital, New Taipei City, Taiwan 13 Department 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 15 Ph.D. Program in Medicine Biotechnology, College of Medicine, Taipei Medical University, Taipei, Taiwan 16 Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan 17 Graduate 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.