Abstract
Abstract Studies have shown that vitamin E forms including gamma-tocopherol (≥T), delta-tocopherol (≥T) and especially gamma-tocotrienol (≥TE), a major form of vitamin E in palm oil, exhibited potent anticancer activities in various types of cancer cells. 13′-carboxychromanol (13′-COOH), a long-chain metabolite of αT, has recently been shown to have anti-inflammatory activities and appears to induce apoptosis in certain type of cancer cells. However, the molecular mechanisms of the anticancer effects are not understood. In the current study, we found that 13′-COOH inhibited the growth and induced death of human colon and pancreatic cancer cells in a time- and dose-dependent manner. In these activities, 13′-COOH was more potent than αTE, which is much stronger than αT and αT. Since we have previously shown that αTE and αT induce prostate cancer cell death by modulation of sphingolipid metabolism, we investigated whether αTE and 13′-COOH have effects on sphingolipids using liquid chromatography tandem mass spectrometry. Treatment of HCT116 cells with αTE or 13′-COOH significantly increased dihydroceramides and dihydrosphingosine, two sphingoid bases in de novo synthesis pathway of sphingolipids. In contrast, sphingomyelins and ceramides remained largely unchanged after treatment. This accumulation of intracellular dihydroceramides and no apparent change of sphingomyelins suggest potential inhibition of dihydroceramide desaturase (DEGS) enzyme by these compounds. Consistently, we found that αTE inhibited the DEGS activity in a time- and dose-dependent manner in an in situ assay, while it did not have any effect on DEGS expression. These results indicate that αTE and 13′-COOH interrupt de novo synthesis of sphingolipids, which play a role in regulating cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2592. doi:1538-7445.AM2012-2592
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