Pectin-enriched diet affects distribution and expression of apoptosis-cascade proteins in colonic crypts of dimethylhydrazine-treated rats

Carmel Avivi-Green, Zecharia Madar, Betty Schwartz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The colonic crypt contains highly proliferative cells in its base and differentiated cells on its luminal surface. Carcinogenesis significantly affects this orderly cellular distribution. The aims of this study were: i) to examine the expression of apoptosis-related proteins along the crypt-lumen axis during 1,2-dimethylhydrazine (DMH)-induced carcinogenesis, ii) to assess whether a diet supplemented with the soluble fiber pectin affects those parameters, in comparison to non-carcinogen-treated rats and in relation to rats fed a standard diet and treated with DMH. The pectin-enriched diet induced upregulation of active caspase-1 subunit (20 kDa) and of caspase-3 precursor in DMH-treated rats. Pectin enhanced caspase-3 activity in all colonocyte populations, in both non- DMH and DMH-treated rats. The luminal colonocytes exhibited higher caspase-3 activity than proliferative colonocytes of rats fed a standard diet in non-DMH and DMH-treated rats, whereas in pectin-fed non-DMH-treated rats, equal activity was measured among all colonocyte populations. In the DMHtreated rats, the cleaved poly(ADP-ribose) polymerase subunit (89 kDa) was detected in luminal colonocytes of rats fed pectin and was higher than in rats fed the standard diet. Bak was equally expressed in isolated colonocytes from rats of both dietary groups treated with DMH and in the normal rats fed pectin, whereas in the non-DMH-treated rats fed a standard diet, higher expression was obtained in differentiated colonocytes. In the DMH-treated rats, Bcl-2 expression was lower in all colonocytes harvested from rats fed pectin, relative to rats fed the standard diet. Apoptotic index in the DMH-treated groups was higher in rats receiving the pectin diet compared with the standard diet in both the differentiated cell populations and the proliferating colonocytes. Average tumor number and volume per rat were lower in rats fed pectin. These findings indicate that dietary fibers regulate expression, function and distribution of apoptotic-related proteins in the crypt during colon carcinogenesis, changes that probably induce a reduction in tumor volume. We assume that butyrate, produced following fermentation of pectin, may play a key role in these effects.

Original languageAmerican English
Pages (from-to)689-698
Number of pages10
JournalInternational Journal of Molecular Medicine
Volume6
Issue number6
DOIs
StatePublished - Dec 2000

Bibliographical note

Publisher Copyright:
© 2000 Spandidos Publications. All rights reserved.

Keywords

  • Apoptosis
  • Caspase
  • Colon cancer
  • Short-chain fatty acids
  • Soluble fiber

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