Propionibacterium freudenreichii selectively induces apoptosis of cancer, but not healthy, colon epithelial cells. - Université de Rennes Accéder directement au contenu
Communication Dans Un Congrès Année : 2010

Propionibacterium freudenreichii selectively induces apoptosis of cancer, but not healthy, colon epithelial cells.

Résumé

Colorectal cancer constitutes a major concern in developed countries and is tightly linked to environmental factors such as diet. Modification of the diet, including heavily roasted red meat and excess of fat, is in particular regarded as responsible for an increased cancer occurrence. Several studies suggest that it may be avoided via modulation of the diet, including the use of probiotics and prebiotics. Short chain fatty acids (SCFA, mainly butyrate, provided through dietary fibres) play a central protective role in this context and were shown to favour apoptosis of colon cancer cells, yet growth and differentiation of healthy ones. SCFA result mainly from bacterial fermentation of carbohydrates in the intestine and would be responsible for the preventive effect of dietary fibres. However, not all studies support a chemopreventive effect of SCFA, because of a lack of agreement between in vivo and in vitro studies. Dairy propionibacteria constitute promising probiotics in this context and release SCFA, mainly propionate and acetate, in their microenvironment. Indeed, SCFA constitute the final products of their peculiar obligatory fermentation. We have shown that this fermentation occurs within the gut, leading to enhanced intraluminal concentrations of SCFA. Propionibacterial SCFA induce in vitro apoptosis of colon cancer cells (HT-29, Caco-2) through a mitochondriotoxic effect of SCFA and may thus prove useful in the prophylaxis of colorectal cancer. METHODS Propionibacterial SCFA were used to treat both malignant human colorectal cancer cells HT-29 and normal healthy human colonocytes HIEC. Viability was monitored and apoptosis quantified by Hoescht staining and caspases activity assay. Human microbiota associated rats were fed with propionibacteria. The rats were either treated with 1,2-dimethylhydrazine (DMH) or not. Apoptosis and proliferation were quantified in the rats colon using TUNEL and PCNA labelling, respectively. RESULTS We report here a specific pro-apoptotic effect of dairy propionibacteria. Normal human intestinal epithelial crypt cells HIEC, used as a model of non-cancer cells, were much less susceptible to apoptosis induction by propionibacteria than malignant proliferative HT-29 cells, suggesting a differential sensitivity between normal and transformed cells. Accordingly, specific apoptosis induction by propionibacteria was evidenced in rats treated with the carcinogen 1,2-dimethylhydrazine (DMH). In these mutagenised rats, proliferation was furthermore reduced by the presence of propionibacteria in their diet. By contrast, propionibacteria had no effect in healthy control rats, neither on proliferation, nor on apoptosis, at the level of intestinal mucosa. DISCUSSION Altogether, these data indicate that probiotic products containing dairy propionibacteria should be considered as part of a preventive diet for the prevention of colorectal cancer or as a dietary supplement used in conjunction with chemotherapy
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Dates et versions

hal-01454359 , version 1 (02-02-2017)

Identifiants

  • HAL Id : hal-01454359 , version 1
  • PRODINRA : 200576

Citer

Gwénaël Jan, Fabien Cousin, Annaïg Lan, Elodie Jouan, Sylvie Rabot, et al.. Propionibacterium freudenreichii selectively induces apoptosis of cancer, but not healthy, colon epithelial cells.. International Scientific Conference on Probiotics and Prebiotics - IPC2010, Jun 2010, Kosicé, Slovakia. ⟨hal-01454359⟩
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