Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats

  • Authors:
    • Asher Begleiter
    • Kosala Sivananthan
    • Georgia M. Lefas
    • Andrew W. Maksymiuk
    • Ranjana P. Bird
  • View Affiliations

  • Published online on: June 1, 2009     https://doi.org/10.3892/or_00000388
  • Pages: 1559-1565
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Abstract

Inducers of phase II detoxifying enzymes have been studied as chemopreventive agents for a variety of cancers. Phase II detoxifying enzymes may play a significant role in preventing carcinogen-induced colon cancer at the initiation and post-initiation stage, but the contribution of NAD(P) H:quinone oxidoreductase 1 (NQO1) to this effect remains unclear. Using the carcinogen-induced colon cancer Sprague-Dawley rat model, we previously showed that oltipraz selectively induces NQO1 in the colons of these rats without inducing other phase II detoxifying enzymes. We demonstrated that selective induction of NQO1 in the rat colon prior to treatment with a carcinogen significantly inhibited the formation of aberrant crypt foci (ACF). Using the same rat model, we found that rats fed oltipraz containing diet following treatment with the colon carcinogen, azoxymethane (AOM), had 60% fewer ACF after 12 weeks compared with rats fed a control diet. In addition, rats fed oltipraz containing diet after AOM treatment developed 40% fewer colon adenomas and fewer colon tumors than rats fed a control diet. There was also a 60% increase in the percentage of apoptotic cells in ACF from oltipraz fed rats compared with ACF from control fed rats. Together, these results suggest that NQO1 can contribute to inhibition of colon carcinogenesis at the post-initiation stage. A possible mechanism for this effect may be that induction of NQO1 increases apoptosis in carcinogen initiated colonic epithelial cells that prevents these cells from progressing to a neoplastic state. Thus, NQO1 may be an important target for chemoprevention of colon cancer.

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June 2009
Volume 21 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Begleiter A, Sivananthan K, Lefas GM, Maksymiuk AW and Bird RP: Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats. Oncol Rep 21: 1559-1565, 2009.
APA
Begleiter, A., Sivananthan, K., Lefas, G.M., Maksymiuk, A.W., & Bird, R.P. (2009). Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats. Oncology Reports, 21, 1559-1565. https://doi.org/10.3892/or_00000388
MLA
Begleiter, A., Sivananthan, K., Lefas, G. M., Maksymiuk, A. W., Bird, R. P."Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats". Oncology Reports 21.6 (2009): 1559-1565.
Chicago
Begleiter, A., Sivananthan, K., Lefas, G. M., Maksymiuk, A. W., Bird, R. P."Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats". Oncology Reports 21, no. 6 (2009): 1559-1565. https://doi.org/10.3892/or_00000388