HSP90 expression and its association with wighteone metabolite response in HER2-positive breast cancer cells

Abstract

Abstract.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 tree Erythrina 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.

Inhibition of heat shock protein 90 exerts an antitumour effect in angiosarcoma: involvement of the vascular endothelial growth factor signalling pathway

“…HSP90 is a molecular chaperone protein that is essential for the maintenance and progression of cancer . In addition, overexpression of HSP90 is reported in several malignancies and is correlated with a poor prognosis . Our results showed that HSP90 was overexpressed in angiosarcoma cell lines in vitro and in tissues derived from patients with angiosarcoma.…”

“…10 In addition, overexpression of HSP90 is reported in several malignancies [33][34][35] and is correlated with a poor prognosis. 33,36 Our results showed that HSP90 was overexpressed in angiosarcoma cell lines in vitro and in tissues derived from patients with angiosarcoma.…”

Erythrina suberosa: Ethnopharmacology, Phytochemistry and Biological Activities

“…They showed that both MLF and AIF demonstrated the most potent cytotoxicity with IC 50 of~20 µM in HL60 cells and could induce apoptosis through inhibition of NF-kB factor (through the signal transducer of activation (STAT) pathway) [3]. Moreover, wighteone, an isoflavone derived from E. suberosa stem bark as mentioned above, demonstrated anticancer effects in MCF-7 HER2-positive cells (human mammary cancer cells) mediated by the heat shock protein 90 (HSP90), again increasing apoptosis and reducing cell proliferation [29]. Is it notable that wighteone can be found in different plants: Cudrania tricuspidata (Carrière) Bureau, Ficus tikoua Bur., Maclura pomifera (Raf.)…”

The Association Between HSP90/topoisomerase I Immunophenotype and the Clinical Features of Colorectal Cancers in Respect to KRAS Gene Status

“…Xu et al (16) and Ahn et al (21) demonstrated that high HSP90 protein expression is related to the metastasis and invasion of CRC. Preclinical studies and early clinical trials have confirmed the efficacy of HSP90 inhibition as a target therapy for many solid tumors (6,16,19,20). Recent data showed the therapeutic utility of HSP90 inhibitors in patients resistant to tyrosine kinase inhibitors (7,18).…”

“…Many HSP90 client proteins are involved in processes such as proliferation, apoptosis, and cycle progression (16,18). Several reports have analyzed HSP90 expression in solid tumors and found that HSP90 expression is correlated with clinical prognosis, (5,16,19,20). Xu et al (16) and Ahn et al (21) demonstrated that high HSP90 protein expression is related to the metastasis and invasion of CRC.…”