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Related Experiment Videos

Histone deacetylase inhibitors decrease proliferation and modulate cell cycle gene expression in normal mammary

T Davis1, C Kennedy, Y E Chiew

  • 1Department of Gynaecological Oncology, Westmead Hospital, University of Sydney, Westmead, NSW, Australia.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|December 6, 2000
PubMed
Summary
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Butyrate and its derivatives inhibit breast cancer cell growth and promote differentiation. These findings suggest potential for breast cancer prevention in high-risk women.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Full-term pregnancy early in reproductive life is protective against breast cancer.
  • Parity's protective effects are linked to differentiation, hormone receptor levels, and hormone sensitivity.
  • Butyrate, a short-chain fatty acid, induces differentiation and inhibits proliferation in breast cancer cells.

Purpose of the Study:

  • To investigate the effects of butyrate on normal human breast epithelial cells.
  • To compare butyrate with its derivatives, phenylacetate and phenylbutyrate, for breast cancer prevention potential.

Main Methods:

  • Treatment of normal and breast cancer cell lines (MCF-7, MDA-MB-231) with butyrate, phenylacetate, and phenylbutyrate.
  • Assessed cell proliferation, differentiation (lipid droplet accumulation), and expression of estrogen receptor (ER) mRNA, cyclin D1, p21(Waf1/Cip1), and pRB.

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Main Results:

  • All agents demonstrated concentration-dependent growth inhibition in tested cell lines.
  • Phenylbutyrate and butyrate showed similar antiproliferative effects; phenylacetate was less effective.
  • Agents induced differentiation in normal and malignant breast cells and decreased ER mRNA in MCF-7 cells.

Conclusions:

  • Butyrate and its derivatives reduce proliferation and induce differentiation in both normal and malignant breast cells.
  • Modulation of cyclin D1 expression is implicated in the antiproliferative effects of butyrates.
  • These compounds are potential chemopreventive agents for women at high risk of breast cancer.