HSP90 expression and its association with wighteone metabolite response in HER2-positive breast cancer cells.
It is well known that heat shock protein 90 (HSP90) overexpression is correlated with poor prognosis and chemo-resistance in human malignant cancers. At the same time, wighteone, or 6-prenyl-5,7,4'-trihydroxyisoflavone, a major isoflavone component of the ornamental tall treeErythrina suberosa, has been demonstrated to exhibit a potent anti-proliferative effect on human leukemia HL-60 cancer cell lines. In this study, the effects of wighteone on the proliferation of HER2-positive breast cancer cells were investigated, and the action mechanism was explored. MCF-7 HER2-positive breast cancer cells were treated with various concentrations of wighteone. The growth inhibitory rate of the cells was calculated by MTT assay, apoptosis was detected by flow cytometry, and the expression level of HSP90 was assessed by western blot analysis. The addition of wighteone at concentrations ranging from 1-10 g/ml in the medium for 48 h had a marked inhibition on the proliferation of HER2-positive cancer cell lines. The growth inhibitory rates with 0.5, 2 or 8 mM wighteone were significantly higher compared with the control group. Apoptosis in the wighteone-treated cells was also significantly higher compared with the control group. The expression level of HSP90 in the wighteone group was significantly lower than that in the control group. Our findings demonstrated that wighteone effectively inhibited the proliferation of HER2-positive cancer cell lines, and this is considered to be the result of downregulating HSP90 receptor and downstream signaling.
Department of Thyroid, Breast, Hernia and Vascular Surgery, The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia Autonomous Region 010017, P.R. China.
Zhong-Wei
ZW
Cao
Department of Neurology, The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia Autonomous Region 010017, P.R. China.
Qian
Q
Zeng
Department of Thyroid, Breast, Hernia and Vascular Surgery, The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia Autonomous Region 010017, P.R. China.
Hai-Jiang
HJ
Pei
Department of Thyroid, Breast, Hernia and Vascular Surgery, The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia Autonomous Region 010017, P.R. China.
Li-Dong
LD
Ren
Department of Thyroid, Breast, Hernia and Vascular Surgery, The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia Autonomous Region 010017, P.R. China.
Hai-Zhen
HZ
Bai
Department of Thyroid, Breast, Hernia and Vascular Surgery, The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia Autonomous Region 010017, P.R. China.
Ri-Na
RN
Na
apoptosis; breast cancer; metabolite; protein expression; wighteone