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.
Highlights
These studies indicate that using α-TP or its analogs (e.g., α-tocopheryl succinate (α-TOS)) as dietary supplements may be beneficial during chemotherapeutic protocols for patients with breast cancer via a Tocopherol-associated protein (TAP) activation mechanism
A Database for Annotation, Visualization and Integrated Discovery (DAVID) heat map identified the top 26 genes that were up- and down-regulated by α-TOS exposure and functionally clustered into common gene ontology (GO) terms (Figure 2A, Supplementary Table 2)
The clustered genes were related to cellular movement or metastasis [18], cell cycle regulation, signaling transduction [19], death/apoptosis, and growth [20]
Summary
As a cellular binding protein for α-TP and α-TOS, tocopherolassociated protein (TAP) is believed to play an important molecular role in anti-cancer mechanisms in prostate, breast, liver, and brain tissues [6] but is nearly undetectable in most human tissues [7]. We previously showed that TAP was consistently preferentially expressed in normal breast tissue rather than in tumor lesions [8]. These studies indicate that using α-TP or its analogs (e.g., α-TOS) as dietary supplements may be beneficial during chemotherapeutic protocols for patients with breast cancer via a TAP activation mechanism
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