RRR-á-Tocopheryl Succinate Induction of DNA Synthesis Arrest of Human MDA-MB-435 Cells Involves TGF-â-Independent Activation of p21Waf1/Cip1 Weiping Yu ; Bob G. Sanders ; Kimberly Kline Abstract: RRR-á-tocopheryl succinate (vitamin E succinate, VES), a derivative of vitamin E, is a potent antitumor agent. Cellular events involved in VES-induced DNA synthesis arrest of human MDA-MB-435 breast cancer cells were studied. VES induces a dose- and time-dependent inhibition of DNA synthesis and a G0/G1 cell cycle arrest. VES induces expression of p21Waf1/Cip1 mRNA and protein, and antisense oligomers to p21 block VES-induced growth arrest. Evidence suggesting that VES modulates p21 expression in a transforming growth factor-â (TGF-â)-independent fashion includes failure of TGF-â-neutralizing antibodies to block VES-induced DNA synthesis arrest or VES activation of a p21 promoter-regulated reporter gene; VES is not capable of inducing the translocation of green fluorescent protein-Smad2 into the nucleus and is not capable of stimulating a TGF-â-dependent reporter gene, and VES induces growth inhibition and upregulates p21 mRNA levels in TGF-â receptor-defective cells. Nutrition and Cancer Volume: 43 Number: 2 Page: 227 -- 236 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.