Advertisement

Topics

4-Hydroxy-2(E)-nonenal Metabolism Differs in Apc(+/+) Cells and in Apc(Min/+) Cells: It May Explain Colon Cancer Promotion by Heme Iron.

Summary of "4-Hydroxy-2(E)-nonenal Metabolism Differs in Apc(+/+) Cells and in Apc(Min/+) Cells: It May Explain Colon Cancer Promotion by Heme Iron."

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.

Affiliation

INRA UMR1331, TOXALIM (Research Center in Food Toxicology), Université de Toulouse , ENVT, INP, UPS, ToxAlim, 180 chemin de Tournefeuille, F-31027 Toulouse, France.

Journal Details

This article was published in the following journal.

Name: Chemical research in toxicology
ISSN: 1520-5010
Pages: 1984-93

Links

DeepDyve research library

PubMed Articles [28342 Associated PubMed Articles listed on BioPortfolio]

Regulators of glucose metabolism in CD4(+) and CD8(+) T cells.

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...

Treatment of colon cancer with oncolytic herpes simplex virus in preclinical models.

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 ...

Melatonin Cytotoxicity Is Associated to Warburg Effect Inhibition in Ewing Sarcoma Cells.

Melatonin kills or inhibits the proliferation of different cancer cell types, and this is associated with an increase or a decrease in reactive oxygen species, respectively. Intracellular oxidants ori...

Data for comparative proteomics analysis of the antitumor effect of CIGB-552 peptide in HT-29 colon adenocarcinoma cells.

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...

Luteolin and Apigenin Attenuate 4-Hydroxy-2-Nonenal-Mediated Cell Death through Modulation of UPR, Nrf2-ARE and MAPK Pathways in PC12 Cells.

Luteolin and apigenin are dietary flavones and exhibit a broad spectrum of biological activities including antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. The lipid peroxidati...

Clinical Trials [10539 Associated Clinical Trials listed on BioPortfolio]

Neoadjuvant FOLFOX Plus Bevacizumab Chemotherapy in Patients With Locally Advanced Colon Cancer

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...

Snooze Control: Sleep Duration & Glucose Metabolism

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 ...

Combination Chemotherapy With or Without Cetuximab in Treating Patients With Stage III Colon Cancer That Was Completely Removed By Surgery

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...

Vaccine Therapy in Treating Patients With Stage II or Stage III Colon Cancer That Has Been Removed During Surgery

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...

Fluorouracil and Leucovorin and/or Levamisole After Surgery In Treating Patients With Dukes' B Or Dukes' C Colon Cancer

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...

Medical and Biotech [MESH] Definitions

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.

Quick Search
Advertisement
 


DeepDyve research library

Searches Linking to this Article