Apigenin suppresses cancer cell growth through ERbeta.
Journal: 2007/January - Neoplasia
ISSN: 1476-5586
Abstract:
Two flavonoids, genistein and apigenin, have been implicated as chemopreventive agents against prostate and breast cancers. However, the mechanisms behind their respective cancer-protective effects may vary significantly. The goal of this study was to determine whether the antiproliferative action of these flavonoids on prostate (DU-145) and breast (MDA-MB-231) cancer cells expressing only estrogen receptor (ER) beta is mediated by this ER subtype. It was found that both genistein and apigenin, although not 17beta-estradiol, exhibited antiproliferative effects and proapoptotic activities through caspase-3 activation in these two cell lines. In yeast transcription assays, both flavonoids displayed high specificity toward ERbeta transactivation, particularly at lower concentrations. However, in mammalian assay, apigenin was found to be more ERbeta-selective than genistein, which has equal potency in inducing transactivation through ERalpha and ERbeta. Small interfering RNA-mediated downregulation of ERbeta abrogated the antiproliferative effect of apigenin in both cancer cells but did not reverse that of genistein. Our data unveil, for the first time, that the anticancer action of apigenin is mediated, in part, by ERbeta. The differential use of ERalpha and ERbeta signaling for transaction between genistein and apigenin demonstrates the complexity of phytoestrogen action in the context of their anticancer properties.
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Neoplasia 8(11): 896-904

Apigenin Suppresses Cancer Cell Growth through ERβ<sup><a href="#FN1" rid="FN1" class=" fn">1</a></sup>

Department of Surgery, University of Massachusetts Medical School, Worcester, MA 01605, USA
Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA
Address all correspondence to: Shuk-Mei Ho, PhD, Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH 45267. E-mail: ude.cu@oh.iem-kuhs
Address all correspondence to: Shuk-Mei Ho, PhD, Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH 45267. E-mail: ude.cu@oh.iem-kuhs
Received 2006 Aug 2; Revised 2006 Sep 13; Accepted 2006 Sep 13.

Abstract

Two flavonoids, genistein and apigenin, have been implicated as chemopreventive agents against prostate and breast cancers. However, the mechanisms behind their respective cancer-protective effects may vary significantly. The goal of this study was to determine whether the antiproliferative action of these flavonoids on prostate (DU-145) and breast (MDA-MB-231) cancer cells expressing only estrogen receptor (ER) β is mediated by this ER subtype. It was found that both genistein and apigenin, although not 17β-estradiol, exhibited antiproliferative effects and proapoptotic activities through caspase-3 activation in these two cell lines. In yeast transcription assays, both flavonoids displayed high specificity toward ERβ transactivation, particularly at lower concentrations. However, in mammalian assay, apigenin was found to be more ERβ-selective than genistein, which has equal potency in inducing transactivation through ERα and ERβ. Small interfering RNA-mediated downregulation of ERβ abrogated the antiproliferative effect of apigenin in both cancer cells but did not reverse that of genistein. Our data unveil, for the first time, that the anticancer action of apigenin is mediated, in part, by ERβ. The differential use of ERα and ERβ signaling for transaction between genistein and apigenin demonstrates the complexity of phytoestrogen action in the context of their anticancer properties.

Keywords: Phytoestrogens, genistein, ERα, apoptosis, cancer chemoprevention
Abstract

Acknowledgement

We thank Irving Chung for editing the manuscript.

Acknowledgement

Footnotes

This research was supported, in part, by National Institute of Health grants DK61084, CA112532, CA15776, and ES013071, and Department of Defense grant DAMD-W81XWH-04-1-0165.

Footnotes

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