Cytotoxicity of alpha-tocopheryl succinate, malonate and oxalate in normal and cancer cells in vitro and their anti-cancer effects on mouse melanoma in vivo

Journal of Nutritional Science and Vitaminology
Kentaro KogureKenji Fukuzawa

Abstract

alpha-Tocopheryl succinate (TS), which is known to induce apoptosis selectively in cancer cells, has attracted attention as a chemotherapeutic agent. Recently, we found that alpha-tocopheryl malonate (TM) and alpha-tocopheryl oxalate (TO), among the alpha-tocopheryl esters tested, have high apoptogenic activity as well as TS. In this study, we investigated the characteristics of their cytotoxicity on normal cells and cancer cells in vitro, and their anti-cancer effects on mice inoculated with melanoma B16-F1 cells in vivo. The order of in vitro cytotoxicity was TO > or = TM > TS in all cell lines examined. Addition of exogenous superoxide dismutase (SOD) and the antioxidant N-acetyl cysteine (NAC) inhibited TS- and TM- but not TO-induced cell deaths. A selective cytotoxic effect on cancer cells was observed with TS but not with TM or TO. c-Jun N-terminal kinase (JNK) inhibitor II prevented cell death induced by TS but did not prevent cell deaths induced either by TM or TO. Intravenous administration of vesiculated TS and TM to mice inoculated with melanoma B16-F1 cells prevented tumor growth and enhanced the mean survival time, but TO administration killed the mice due to its acute high toxicity. From these results, we discusse...Continue Reading

Citations

Apr 12, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Stepan KoudelkaJaroslav Turanek
Nov 5, 2016·International Journal of Pharmaceutics·Yanan GaoJingling Tang
Dec 17, 2008·Molecular Nutrition & Food Research·Yan ZhaoKun Wu
May 28, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sri Nurestri Abdul MalekHashim Yaacob
May 30, 2019·Nutrition & Metabolism·Maria Neve OmbraUNKNOWN Italian Melanoma Intergroup (IMI)
Jun 21, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Grażyna NeunertKrzysztof Polewski
Jan 5, 2021·Biological & Pharmaceutical Bulletin·Dai MajimaKentaro Kogure
Oct 12, 2018·Chemistry and Physics of Lipids·Grażyna NeunertKrzysztof Polewski
May 15, 2007·Molecular Aspects of Medicine·Jiri NeuzilStephen J Ralph

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