Biological Functions of α-Tocopheryl Succinate

Abstract

a-Tocopheryl succinate (TS) is a succinic acid ester of a well-known natural antioxidant a-tocopherol (a-T). Physicochemical characteristics of TS are entirely different from the original compound aT. TS becomes vesicles via forming a lamella structure. Furthermore, although the antioxidative activity of aT is lacked by esterification of phenolic hydroxyl (OH) moiety with succinate, TS has versatile biological functions, such as inhibition of cholinesterase activity, inhibition of nuclear factor-kappa B (NF-kB) activation, enhancement of lipopolysaccharide-induced nitric oxide production, and anticancer effect. Especially, we expect TS as a novel anticancer agent. TS nanovesicle shows significant anticancer activity in vitro and in vivo. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces superoxide which mediates the anticancer activity of TS. Moreover, it suggests that TS activates protein kinase C via direct interaction. Based on the analysis of structure and activity relationship, it ensures that succinate moiety of TS plays a vital role in anticancer activity. This review introduces the detail and mechanism of versatile biological functions of TS.

Suppression of Lipid Accumulation in 3T3-L1 Adipocytes by α-Tocopheryl Succinate

“…3c). TS was previously shown to damage fibroblasts and various cancer cells, 3,11) but here we showed that TS is not toxic to adipocytes, at least under the conditions examined. This result indicates that the inhibitory effect of TS on lipid accumulation was not due to cytotoxic effects.…”

“…TS lacks antioxidative activity but retains various biological activities, such as inhibition of cholinesterase, inhibition of nuclear factor-kappa B (NF-κB) activation, and enhancement of lipopolysaccharideinduced nitric oxide production, in addition to anticancer effects. 3) In particular, TS is thought to activate the cell signaling enzyme protein kinase C (PKC) 4) through direct interactions. 5) Since adipogenesis is regulated by various cell signaling pathways, 6,7) we expected that TS could affect lipid accumulation by regulating cell signaling pathways in adipocytes.…”

Depicting the landscape of gut microbial-metabolic interaction and microbial-host immune heterogeneity in deficient and proficient DNA mismatch repair colorectal cancers

“…The dMMR-enriched D-alpha-tocopherol succinate, the most effective analog of vitamin E, presented multiple biological functions, including chemopreventative and anticancer activity. 41 To explore the role of microbiota in the metabolic process, we performed a Spearman’s correlation of differential microbiota and metabolites ( figure 3D ). Notably, the dMMR-enriched RA was mainly correlated with B. velezensis while the dMMR-depleted lactate was negatively correlated with most differential species.…”

Synthesis and Biological Evaluation of α-Tocopherol Derivatives as Potential Anticancer Agents

“…Its pro-apoptotic activity was detected in various epithelial cancer cell types, particularly in breast, colon, and prostate cancers [6][7][8][9]. Significant anticancer activity show TS nanovesicles, both in vitro and in vivo [10]. However, α-TS is effective only by intraperitoneal injection, not by oral administration, since it is hydrolyzed by nonspecific esterases in the intestinal tract and in normal cells [11].…”