The suppression of aberrant crypt multiplicity in colonic tissue of 1,2-dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes
| Autor: | Daniela Diehl, Isabel Winkelmann, Hannelore Daniel, Doris Oesterle, Uwe Wenzel |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Proteome Ratón Citric Acid Cycle Flavonoid Crypt Pharmacology Biology Mice chemistry.chemical_compound In vivo Cell Line Tumor Animals Anticarcinogenic Agents Humans Intestinal Mucosa Carcinogen chemistry.chemical_classification General Medicine Flavones In vitro 1 2-Dimethylhydrazine Diet Mice Inbred C57BL Biochemistry chemistry Colonic Neoplasms Carcinogens Precancerous Conditions Aberrant crypt foci |
| Zdroj: | Carcinogenesis. 28:1446-1454 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgm040 |
| Popis: | Colorectal cancer is the second leading cause of cancer deaths worldwide with diet playing a prominent role in disease initiation and progression. Flavonoids are secondary plant compounds that are suggested as protective ingredients of a diet rich in fruits and vegetables. We here tested whether flavone, a flavonoid that proved to be an effective apoptosis inducer in colon cancer cells in culture, can affect the development of aberrant crypt foci (ACFs) in C57BL/6J mice in vivo when preneoplastic lesions were induced by the carcinogen 1,2-dimethylhydrazine (DMH). Flavone applied at either a low dose (15 mg/kg body wt per day) or a high dose (400 mg/kg body wt per day) reduced the numbers of ACFs significantly, independent of whether it was supplied simultaneously with the carcinogen (blocking group) or subsequent to the tumor induction phase (suppressing group). Proteome analysis performed in colonic tissue samples revealed that flavone treatment increased the expression of a number of Krebs cycle enzymes in the suppressing group and this was associated with reduced crypt multiplicity. It suggests that mitochondrial substrate oxidation is increased by flavone in colonic cells in vivo as already observed in HT-29 cells in vitro as the prime mechanism underlying tumor cell apoptosis induction by flavone. In conclusion, flavone reduces the number of ACFs in DMH-treated mice at doses that can be achieved for flavonoids by a diet rich in fruits and vegetables. Moreover, reduction in crypt multiplicity by flavone is most probably due to the preservation of a normal oxidative metabolism. |
| Databáze: | OpenAIRE |
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