α-Tocopherol phosphate is a water-soluble form of α-tocopherol. α-Tocopherol phosphate functions by scavenging reactive oxygen species and regulating gene expression. α-Tocopherol phosphate can also inhibit tumor cell proliferation and induce apoptosis by modulating the activity of signaling pathways such as Hedgehog, PI3K/Akt, and Src/STAT3[1-2]. α-Tocopherol phosphate can be used in research related to antioxidation and cardiovascular diseases[3-4].
In vitro, ALDH+ MDA-MB-231 cells were co-treated with α-Tocopherol phosphate (100μM) and PS-T for 24 hours. α-Tocopherol phosphate reversed the PS-T-induced increase in lipid oxidation and malondialdehyde concentration, and prevented the inhibitory effects of PS-T on colony formation and mammosphere formation[5]. U87MG and U251 glioblastoma cells were treated with α-Tocopherol phosphate (5μM) and ferrostatin-1 for 24 hours. α-Tocopherol phosphate blocked the NKAP knockdown-induced slowdown in cell proliferation and reversed the increased cell death, apoptosis rate, and lactate dehydrogenase release caused by NKAP knockdown[6].
In vivo, SKG/Jcl mice with laminarin-induced rheumatoid arthritis were intraperitoneally administered α-Tocopherol phosphate (100mg/kg; three times a week for 7 weeks). α-Tocopherol phosphate suppressed edema in the paws and joints, improved the arthritis score, and inhibited pannus formation[7]. Male Swiss mice received a single intracerebroventricular injection of α-Tocopherol phosphate (0.1 or 1nmol/site; 3μL). Two days after the injection, α-Tocopherol phosphate reduced the expression of glutathione reductase and peroxiredoxin 2, and decreased glutathione reductase activity in the hippocampus and cerebral cortex[8].
References:
[1] Saleh MM, Lawrence KP, Jones SA, et al. The photoprotective properties of α-tocopherol phosphate against long-wave UVA1 (385 nm) radiation in keratinocytes in vitro. Sci Rep. 2021 Nov 17;11(1):22400.
[2] Wu Z, Zheng X, Meng L, et al. α-Tocopherol, especially α-tocopherol phosphate, exerts antiapoptotic and angiogenic effects on rat bone marrow-derived endothelial progenitor cells under high-glucose and hypoxia conditions. J Vasc Surg. 2018 Apr;67(4):1263-1273.e1.
[3] Li X, Liao XQ, Chen WR, et al. Paeonol Inhibits Cell Growth by Inducing Ferroptosis in Human Glioma Cells. Pharmacol Res Perspect. 2026 Feb;14(1):e70213.
[4] Nishio K, Ishida N, Saito Y, et al. α-Tocopheryl phosphate: uptake, hydrolysis, and antioxidant action in cultured cells and mouse. Free Radic Biol Med. 2011 Jun 15;50(12):1794-800.
[5] Zhou L, Wu Z, Luo K, et al. Polysaccharides from Huaier induce autophagy-dependent ferroptosis to inhibit breast cancer stem cells in triple-negative breast cancer. Cancer Cell Int. 2025 Dec 10;26(1):13.
[6] Sun S, Gao T, Pang B, et al. RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an m6A-dependent manner. Cell Death Dis. 2022 Jan 21;13(1):73.
[7] Hama S, Kirimura N, Obara A, et al. Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic Symptoms in Mice. Molecules. 2022 Feb 20;27(4):1425.
[8] Uchoa MF, de Souza LF, Dos Santos, et al. Modulation of Brain Glutathione Reductase and Peroxiredoxin 2 by α-Tocopheryl Phosphate. Cell Mol Neurobiol. 2016 Aug;36(6):1015-1022.