Animal and epidemiological studies suggest that dietary heme iron would promote colorectal cancer. Oxidative properties of heme could lead to the formation of cytotoxic and genotoxic secondary lipid oxidation products, such as 4-hydroxy-2(E)-nonenal (HNE). This compound is more cytotoxic to mouse wild-type colon cells than to isogenic cells with a mutation on the adenomatous polyposis coli (APC) gene. The latter thus have a selective advantage, possibly leading to cancer promotion. This mutation is an early and frequent event in human colorectal cancer. To explain this difference, the HNE biotransformation capacities of the two cell types have been studied using radiolabeled and stable isotope-labeled HNE. Apc-mutated cells showed better biotransformation capacities than nonmutated cells did. Thiol compound conjugation capacities were higher for mutated cells, with an important advantage for the extracellular conjugation to cysteine. Both cells types were able to reduce HNE to 4-hydroxynonanal, a biotransformation pathway that has not been reported for other intestinal cells. Mutated cells showed higher capacities to oxidize 4-hydroxynonanal into 4-hydroxynonanoic acid. The mRNA expression of different enzymes involved in HNE metabolism such as aldehyde dehydrogenase 1A1, 2 and 3A1, glutathione transferase A4-4, or cystine transporter xCT was upregulated in mutated cells compared with wild-type cells. In conclusion, this study suggests that Apc-mutated cells are more efficient than wild-type cells in metabolizing HNE into thiol conjugates and 4-hydroxynonanoic acid due to the higher expression of key biotransformation enzymes. These differential biotransformation capacities would explain the differences of susceptibility between normal and Apc-mutated cells regarding secondary lipid oxidation products.
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http://dx.doi.org/10.1021/tx2003036 | DOI Listing |
Curr Rheumatol Rep
December 2024
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS-937, Boston, MA, 02215, USA.
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Surgical resection is the only curative treatment for cholangiocarcinoma, but it is often diagnosed at advanced stages, making surgical resection infeasible. Recently, the concept of conversion surgery has expanded the indications for surgical treatment, thanks to advancements in both perioperative management and chemotherapy. However, it remains unclear which patients benefit most from this treatment strategy.
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December 2024
Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, People's Republic of China.
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School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan.
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December 2024
Department of Biotechnology, Science Campus, Alagappa University, Karaikudi, India.
Early childhood caries (ECC), a severe form of dental caries, is exacerbated by the synergistic interaction between Streptococcus mutans and Candida albicans, leading to greater disease severity than their individual effects. This underscores the need for more targeted and potent therapeutic alternatives. Given the promising anti-infective properties of quaternary ammonium surfactants (QAS), this study explores the microbicidal properties of one such QAS, cetyltrimethylammonium chloride (CTAC), against both individual- and dual-species cultures of S.
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