In vitro and in vivo evaluation of anticancer actions of natural and synthetic vitamin e forms

The goal of these studies was to investigate the potential anticancer properties of two naturally occurring plant sources and two manufactured synthetic forms of vitamin E, i. e., RRR-α-tocopherol (αT), RRR-γ-tocopherol (γT), all-rac-α-tocopherol (all-rac-αT), and all-rac-α-tocopheryl acetate (all-rac-αTAc) in breast cancer models. Vitamin E compounds were evaluated in vitro for inhibition of colony formation and induction of apoptosis in human MDA-MB-435 and MCF-7 breast cancer cells and murine 66cl-4 mammary cancer cells and in vivo for ability to reduce tumor growth and lung and lymph node metastases using the transplantable syngeneic BALB/c mouse 66cl-4-GFP mammary cancer model. γT inhibited colony formation and induced apoptosis in all three cancer cell lines. αT and all-rac-αT were less effective and all-rac-αTAc was ineffective. γT-induced apoptosis was correlated with activation of caspases-8 and -9 and down-regulation of protein expression of c-FLIP and survivin. In vivo study 1 analyses showed that all-rac-aT and all-rac-aTAc significantly inhibited tumor growth and inhibited both visible and microscopic size lung metastases. In vivo study 2 analyses showed that αT and γT reduced tumor growth, but only γT reduced tumor growth significantly in comparison to control. In conclusion, synthetic, but not natural, vitamin E exhibits promising anticancer properties in vivo.