Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Apr;6(4):290-8.
doi: 10.1158/1940-6207.CAPR-12-0449-T. Epub 2013 Jan 30.

Defining the role of histone deacetylases in the inhibition of mammary carcinogenesis by dietary energy restriction (DER): effects of suberoylanilide hydroxamic acid (SAHA) and DER in a rat model

Zongjian Zhu  1 , Weiqin Jiang, John N McGinley, Henry J Thompson
Affiliations

Defining the role of histone deacetylases in the inhibition of mammary carcinogenesis by dietary energy restriction (DER): effects of suberoylanilide hydroxamic acid (SAHA) and DER in a rat model

Zongjian Zhu et al. Cancer Prev Res (Phila). 2013 Apr.

Abstract

Dietary energy restriction (DER) inhibits experimentally induced mammary cancer, an effect accompanied by elevated levels of silent information regulator 2 (SIRT1), a class III histone deacetylase (HDAC). However, the effect of DER on targets of other classes of HDACs has not been reported, a highly relevant issue given evidence that HDAC induction favors the development of cancer and tumor growth. Experiments were carried out to determine whether suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor with broad activity, would affect the anti-cancer activity of DER. Female Sprague Dawley rats (n = 30/group) were injected with 1-methyl-1-nitrosourea (50 mg/kg) at 21 days of age and 7 days thereafter were randomized to groups fed: (i) control diet (AIN-93G), (ii) 0.1% SAHA (w/w), (iii) 40% DER, or (iv) 0.1% SAHA + 40% DER. An additional group was fed 0.1% SAHA + 40%DER for 5 weeks and released to control diet for 3 weeks. DER significantly reduced mammary cancer incidence, multiplicity, and cancer burden and prolonged cancer latency (P < 0.01). Cancer inhibition was maintained in SAHA + DER, despite evidence that histone (H2A(Lys9), H2B(Lys5), and H4(Lys5/8/12/16), but not H3(Lys9); P < 0.001) and non-histone protein deacetylation (p53(Lys373) and p53(Lys382); P < 0.001) induced by DER was reversed by SAHA. This indicates that the inhibition of DER of cancer is not dependent on HDAC induction. After releasing rats from DER + SAHA, cancer multiplicity remained lower than control (P < 0.05), consistent with apoptosis-mediated cell deletion. These findings support further investigation of the hypothesis that HDAC induction by DER blunts its anti-carcinogenic impact.

PubMed Disclaimer

Conflict of interest statement

Disclosure of Potential Conflicts of Interest: There are no conflicts of interest.

Conflict of Interest Statement: None.

Figures

Figure 1
Figure 1
Effects of dietary suberoylanilide hydroxamic acid (SAHA) with dietary energy restriction (DER) on body weight gain and the carcinogenic response. (A) Body weight gain. (B) Incidence of palpable mammary cancer. (C) Number of palpable mammary carcinoma number per rat. (D) Tumor weight. For panels A and D, values are means ±SEM, n=30 rats/group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Thompson HJ, McTiernan A. Weight cycling and cancer: weighing the evidence of intermittent caloric restriction and cancer risk. Cancer Prev Res (Phila) 2011;4:1736–42. - PMC - PubMed
    1. Hursting SD, Smith SM, Lashinger LM, Harvey AE, Perkins SN. Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research. Carcinogenesis. 2010;31:83–9. - PubMed
    1. Thompson HJ, Jiang W, Zhu Z. Energetics and Cancer: Exploring a Road Less Traveled. In: McTiernan A, editor. Physical Activity, Dietary Calorie Restriction, and Cancer. 1. Springer Science + Business Media, LLC; 2011. pp. 55–67.
    1. Thompson HJ, McTiernan A. Weight cycling and cancer: weighing the evidence of intermittent caloric restriction and cancer risk. Cancer Prev Res (Phila) 2011;4:1736–42. - PMC - PubMed
    1. International Agency for Research on Cancer. Physical Activity, Weight Control, and Cancer. [8] Lyon: IARC Press; 2002.
    2. Vainio H, Bianchin IF. Cancer Prevention Handbook.

Publication types

MeSH terms