Dataset Information


Vitamin E metabolite 13'-carboxychromanols inhibit pro-inflammatory enzymes, induce apoptosis and autophagy in human cancer cells by modulating sphingolipids and suppress colon tumor development in mice.

ABSTRACT: Vitamin E forms are substantially metabolized to various carboxychromanols including 13'-carboxychromanols (13'-COOHs) that are found at high levels in feces. However, there is limited knowledge about functions of these metabolites. Here we studied ?T-13'-COOH and ?TE-13'-COOH, which are metabolites of ?-tocopherol and ?-tocotrienol, respectively. ?TE-13'-COOH is also a natural constituent of a traditional medicine Garcinia Kola. Both 13'-COOHs are much stronger than tocopherols in inhibition of pro-inflammatory and cancer promoting cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), and in induction of apoptosis and autophagy in colon cancer cells. The anticancer effects by 13'-COOHs appeared to be partially independent of inhibition of COX-2/5-LOX. Using liquid chromatography tandem mass spectrometry, we found that 13'-COOHs increased intracellular dihydrosphingosine and dihydroceramides after short-time incubation in HCT-116 cells, and enhanced ceramides while decreased sphingomyelins during prolonged treatment. Modulation of sphingolipids by 13'-COOHs was observed prior to or coinciding with biochemical manifestation of cell death. Pharmaceutically blocking the increase of these sphingolipids partially counteracted 13'-COOH-induced cell death. Further, 13'-COOH inhibited dihydroceramide desaturase without affecting the protein expression. In agreement with these mechanistic findings, ?TE-13'-COOH significantly suppressed the growth and multiplicity of colon tumor in mice. Our study demonstrates that 13'-COOHs have anti-inflammatory and anticancer activities, may contribute to in vivo anticancer effect of vitamin E forms and are promising novel cancer prevention agents.


PROVIDER: S-EPMC4867259 | BioStudies | 2016-01-01

REPOSITORIES: biostudies

Similar Datasets

2017-01-01 | S-EPMC5635819 | BioStudies
2015-01-01 | S-EPMC4475472 | BioStudies
2017-01-01 | S-EPMC5683003 | BioStudies
2019-01-01 | S-EPMC6678307 | BioStudies
2016-01-01 | S-EPMC5068917 | BioStudies
2016-01-01 | S-EPMC5126122 | BioStudies
1000-01-01 | S-EPMC2900425 | BioStudies
1000-01-01 | S-EPMC4413624 | BioStudies
2020-01-01 | S-EPMC7177910 | BioStudies
2018-01-01 | S-EPMC6148290 | BioStudies