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-alpha-tocopherol (alphaT), RRR-gamma-tocopherol (gammaT), all-rac-alpha-tocopherol (all-rac-alphaT), and all-rac-alpha-tocopheryl acetate (all-rac-alphaTAc) 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. gammaT inhibited colony formation and induced apoptosis in all three cancer cell lines. alphaT and all-rac-alphaT were less effective and all-rac-alphaTAc was ineffective. gammaT-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-alphaT and all-rac-alphaTAc significantly inhibited tumor growth and inhibited both visible and microscopic size lung metastases. In vivo study 2 analyses showed that alphaT and gammaT reduced tumor growth, but only gammaT reduced tumor growth significantly in comparison to control. In conclusion, synthetic, but not natural, vitamin E exhibits promising anti-cancer properties in vivo.
Yu
Weiping
W
Division of Nutrition/A2703, University of Texas at Austin, Austin, TX 78712-1097, USA.
Jia
Li
L
Wang
Pei
P
Lawson
Karla A
KA
Simmons-Menchaca
Marla
M
Park
Sook-Kyung
SK
Sun
Luzhe
L
Sanders
Bob G
BG
Kline
Kimberly
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008207:Lymphatic Metastasis; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D051379:Mice; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives / Q000494:pharmacology
D000970:Antineoplastic Agents; D014810:Vitamin E; D024502:alpha-Tocopherol; D024505:Tocopherols