Inhibition of cell growth by BrMC through inactivation of Akt in HER‑2/neu‑overexpressing breast cancer cells

Cao,Xiao‑Zheng; Xiang,Hong‑Lin; Quan,Mei‑Fang; He,Li‑Hua

doi:10.3892/ol.2014.1889

Inhibition of cell growth by BrMC through inactivation of Akt in HER‑2/neu‑overexpressing breast cancer cells

Authors:
- Xiao‑Zheng Cao
- Hong‑Lin Xiang
- Mei‑Fang Quan
- Li‑Hua He
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Affiliations: Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China
Published online on: February 18, 2014 https://doi.org/10.3892/ol.2014.1889
Pages: 1632-1638

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Abstract

We previously reported that chrysin (ChR) and its analogs induced cell cycle arrest and apoptosis in human estrogen receptor‑positive/‑negative breast cancer cells. However, it was unknown whether 8‑bromo‑7‑methoxychrysin (BrMC), a novel synthetic ChR analog, inhibited the cell growth of human epidermal growth factor receptor 2 (HER‑2)/neu‑overexpressing breast cancers. In the present study, it was demonstrated that BrMC preferentially inhibited the cell viability of HER‑2/neu‑overexpressing MDA‑MB‑453 and BT‑474 cells. Western blot analysis revealed that HER‑2/neu expression and tyrosine phosphorylation were inhibited by BrMC in a concentration‑dependent manner; whereas the proteasome inhibitor, MG‑132, significantly prevented BrMC‑induced HER‑2/neu depletion and cell death in MDA‑MB‑453 cells. This directly indicated that BrMC‑induced HER‑2/neu depletion and cell growth inhibition was mediated by a proteasomal pathway. BrMC significantly downregulated the expression of cyclin D1, cyclin E and CDK4, followed by the suppression of protein kinase B phosphorylation and downstream effectors, GSK‑3β and β‑catenin. A colony formation assay also confirmed the growth‑inhibitory effects of BrMC. Thus, these findings clearly demonstrate the anticancer activity of BrMC against human HER‑2/neu‑overexpressing breast cancer cells. Thus, these findings clearly demonstrate the anticancer activity of BrMC against human HER 2/neu-overexpressing breast cancer cells, and highlight BrMC as a promising candidate for breast cancer therapy.

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