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Cited by 34

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Suppression of Familial Adenomatous Polyposis by CP-31398, a TP53 Modulator, in APCmin/+ Mice

Rao, Chinthalapally V., Swamy, Malisetty V., Patlolla, Jagan M.R., Kopelovich, Levy·2008·Cancer Research
DOI 10.1158/0008-5472.can-08-1610
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Abstract

p53 mutations occur in a large number of human malignancies. Mutant p53 is unable to affect downstream genes necessary for DNA repair, cell cycle regulation, and apoptosis. The styrylquinazoline CP-31398 can rescue destabilized mutant p53 expression and promote activity of wild-type p53. The present study examines chemopreventive effects of CP-31398 on intestinal adenoma development in an animal model of familial adenomatous polyposis. Effects were examined at both early and late stages of adenoma formation. Effects of CP-31398 on early-stage adenomas were determined by feeding 7-week-old female C57BL/6J-APCmin (heterozygous) and wild-type C57BL/6J mice with American Institute of Nutrition-76A diets containing 0, 100, or 200 ppm of CP-31398 for 75 days. To examine activity toward late-stage adenomas, CP-31398 administration was delayed until 15 weeks of age and continued for 50 days. During early-stage intervention, dietary CP-31398 suppressed development of intestinal tumors by 36% (P < 0.001) and 75% (P < 0.0001), at low and high dose, respectively. During late-stage intervention, CP-31398 also significantly suppressed intestinal polyp formation, albeit to a lesser extent than observed with early intervention. Adenomas in treated mice showed increased apoptotic cell death and decreased proliferation in conjunction with increased expression of p53, p21WAF1/CIP, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase. These observations show for the first time that the p53-modulating agent CP-31398 possesses significant chemopreventive activity in vivo against intestinal neoplastic lesions in genetically predisposed APCmin/+ mice. Chemopreventive activity of other agents that restore tumor suppressor functions of mutant p53 in tumor cells is currently under investigation. [Cancer Res 2008;68(18):7670–5]

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Metadata

Authors
Rao, C. V., Swamy, M. V., Patlolla, J. M. R., & Kopelovich, L.
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2008-09-14
Volume
68
Issue
18
Pages
7670-7675
ISSN
  • 0008-5472
  • 1538-7445
DOI
10.1158/0008-5472.can-08-1610
Cited by
34
References
3
Language
en

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CoChat. (2026). Citation check: Suppression of Familial Adenomatous Polyposis by CP-31398, a TP53 Modulator, in APCmin/+ Mice. https://app.cochat.ai/papers/10.1158/0008-5472.can-08-1610
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Rao, C. V., Swamy, M. V., Patlolla, J. M. R., & Kopelovich, L. (2008). Suppression of Familial Adenomatous Polyposis by CP-31398, a TP53 Modulator, in APCmin/+ Mice. Cancer Research. https://doi.org/10.1158/0008-5472.can-08-1610

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