Track topics on Twitter Track topics that are important to you
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.
INRA UMR1331, TOXALIM (Research Center in Food Toxicology), Université de Toulouse , ENVT, INP, UPS, ToxAlim, 180 chemin de Tournefeuille, F-31027 Toulouse, France.
This article was published in the following journal.
Name: Chemical research in toxicology
Much like cancer cells, activated T cells undergo various metabolic changes that allow them to grow and proliferate rapidly. By adopting aerobic glycolysis upon activation, T cells effectively priorit...
Colon cancer can be treated with 5-fluorouracil (5-FU), but 5-FU resistance frequently occurs. We determined whether 5-FU resistance arises as a result of endoplasmic reticulum (ER) stress. 5-FU-resis...
Cancer stem cells (CSCs), which are a rare population in any type of cancer, including colon cancer, are tumorigenic and responsible for cancer recurrence and metastasis. CSCs have been isolated from ...
Cellular senescence is a complex stress response that permanently arrests the proliferation of cells at risk for oncogenic transformation. However, senescent cells can also drive phenotypes associate...
CIGB-552 is a second generation antitumor peptide that displays potent cytotoxicity in lung and colon cancer cells. The nuclear subproteome of HT-29 colon adenocarcinoma cells treated with CIGB-552 pe...
The purpose of this study is to see if giving chemo-therapy for colon cancer before surgery can shrink the cancer and lead to a higher rate of cure than operating first and then giving che...
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, or fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stoppin...
This project investigated how glucose metabolism differs due to sleep deprivation for three consecutive nights as compared to sufficient sleep for three nights by examining concentrations ...
RATIONALE: Vaccines made from a patient's white blood cells and tumor cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy use different ways to...
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Leucov...
The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.
Cells forming a framework supporting the sensory AUDITORY HAIR CELLS in the organ of Corti. Lateral to the medial inner hair cells, there are inner pillar cells, outer pillar cells, Deiters cells, Hensens cells, Claudius cells, Boettchers cells, and others.
An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.
A group of cells that includes FIBROBLASTS, cartilage cells, ADIPOCYTES, smooth muscle cells, and bone cells.
The segment of LARGE INTESTINE between ASCENDING COLON and DESCENDING COLON. It passes from the RIGHT COLIC FLEXURE across the ABDOMEN, then turns sharply at the left colonic flexure into the descending colon.