Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells.

Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Research Abstract Details 

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Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Abstract Text:

Zhiming Mai,George L Blackburn,Jin-Rong Zhou,

Although tamoxifen (TAM) is used for the front-line treatment and prevention of estrogen receptor-positive (ER+) breast tumors, nearly 40% of estrogen-dependent breast tumors do not respond to TAM treatment. Moreover, the positive response is usually of short duration, and most tumors eventually develop TAM-resistance. Overexpression of HER2 gene is associated with TAM-resistance of breast tumor, and suppression of HER2 expression enhances the TAM activity. Soy isoflavone genistein has been shown to have anti-cancer activities and suppress expression of HER2 and ERalpha. The objective of this study was to test the hypothesis that genistein may sensitize the response of ER+ and HER2-overexpressing breast cancer cells to TAM treatment. The combination treatment of TAM and genistein inhibited the growth of ER+/HER2-overexpressing BT-474 human breast cancer cells in a synergistic manner in vitro. Determination of cellular markers indicated that this synergistic inhibitory effect might be contributed in part from combined effects on cell-cycle arrest at G(1) phase and on induction of apoptosis. Further determination of the molecular markers showed that TAM and genistein combination synergistically induced BT-474 cell apoptosis in part by synergistic downregulation of the expression of survivin, one of the apoptotic effectors, and downregulation of EGFR, HER2, and ERalpha expression. Our research may provide a novel approach for the prevention and/or treatment of TAM insensitive/resistant human breast cancer, and warrants further in vivo studies to verify the efficacy of genistein and TAM combination on the growth of ER+/HER2-overexpressing breast tumors and to elucidate the in vivo mechanisms of synergistic actions.

Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Publishing Authors By Initials

Z Mai,GL Blackburn,JR Zhou,

For similar organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, aromatic: benzene derivatives: benzylidene compounds: stilbenes: tamoxifen research abstracts see: organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, aromatic: benzene derivatives: benzylidene compounds: stilbenes: tamoxifen research

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Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular carcinogenesis

VOLUME: 46

Page Numbers: 534-42

Journal Abbreviation: Mol. Carcinog.

ISSN: 0899-1987

DAY: 3

MONTH: Jul

YEAR: 2007

Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Information

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LANGUAGE: eng

NlmUniqueID: 8811105

Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Keywords Mesh Terms:

KEYWORDS: Tamoxifen

MESH TERMS: administration & dosage

Chemical & Substance for Abstract: Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells. Information

Substance Name: Caspases

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells.

AFFILIATION: Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.

Country: United States

AGENCY: United States NCI

GRANT: R03 CA 112644

ACRONYM: CA

MEDLINETA: Mol Carcinog

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