Effects of dehydroepiandrosterone and calorie restriction on the Bcl-2/Bax-mediated apoptotic pathway in p53-deficient mice

Cancer Letters
T T WangJ M Phang

Abstract

Modulation of apoptosis through altered expression of Bcl-2 and/or Bax may be a mechanism by which dehydroepiandrosterone (DHEA) administration and calorie restriction (CR) exert their chemopreventive effects in p53-deficient (p53-/-) mice. Using immunohistochemical detection we found that treatment with both DHEA and CR resulted in decreased expression of the PCNA proliferation marker in the thymus. In addition, treatment with DHEA also increased the rate of apoptosis in the thymus, resulting in marked thymic atrophy. Thus, both DHEA and CR appear to shift cell number homeostasis by favoring apoptosis. To further understand the molecular mechanisms by which DHEA and CR exert their effects, we examined two components of the apoptotic pathway, Bcl-2 and Bax. We found that p53-/- mice have much higher levels of Bcl-2 mRNA in the thymus than wild-type (p53+/+) mice. Treatment of p53-/- animals with DHEA resulted in decreased Bcl-2 but not Bax mRNA levels in the thymus. In contrast, CR did not change either Bcl-2 or Bax mRNA expression. The present study provides molecular evidence that DHEA and CR may modulate tumorigenesis through alterations in the apoptotic and/or proliferative pathways.

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Citations

Jul 2, 1999·Comparative Biochemistry and Physiology. Part C, Pharmacology, Toxicology & Endocrinology·Y R Lea-CurrieM K Mcintosh
Feb 26, 1999·Journal of the National Cancer Institute·S D HurstingJ M Phang
Jun 15, 2007·Acta Tropica·Carla Domingues SantosJosé Clóvis do Prado
Sep 8, 2004·International Immunopharmacology·Jun LiangYayi Hou
Jul 24, 2008·Dose-response : a Publication of International Hormesis Society·Okom Nkili F C Ofodile
Feb 24, 2001·Toxicologic Pathology·S D HurstingB J Davis
Jul 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Madhu MazumdarGeorge J Bosl
May 18, 1999·The Journal of Biological Chemistry·V Budhram-MahadeoD S Latchman
Nov 6, 2001·The Journal of Nutrition·S D HurstingJ C Barrett
Dec 1, 2004·The Journal of Nutrition·Arti C PatelStephen D Hursting
Aug 31, 2004·The Journal of Nutrition·Stephen D HurstingSusan N Perkins

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