Heat Shock Protein as Molecular Targets for Breast Cancer Therapeutics

Kim, Lee Su; Kim, Jun Ho

doi:10.4048/jbc.2011.14.3.167

Cited by 54 publications

(39 citation statements)

References 81 publications

(88 reference statements)

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“…From this, it is clear that wighteone induces MCF-7 cell apoptosis in vitro and restrains cell proliferation. The activation of the AKT and MAPK pathways and the high expression of HSP90 protein are common in HER2-positive breast cancer (27) and there is a positive correlation between HSP90 and breast cancer pathological stage, local recurrence and distant metastasis, all of which result in poor patient prognosis (28). Our study reveals that wighteone blocks the expression of HSP90 protein in MCF-7 cells, and that the inhibitory effect is enhanced with increasing drug concentrations.…”

Section: A B C Dmentioning

confidence: 58%

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

et al. 2016

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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.

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Section: A B C Dmentioning

confidence: 58%

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

et al. 2016

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“…This concept has been evaluated in many cancers [9][10][11][12][13][14][15][16], including numerous attempts in pre-clinical and clinical breast cancer models [17][18][19][20][21][22][23][24][25][26][27] (reviewed in [28]). …”

Section: Discussionmentioning

confidence: 99%

Ratio of proliferation markers and HSP90 gene expression as a predictor of pathological complete response in breast cancer neoadjuvant chemotherapy

Jarząb

Kowal

Bal

et al. 2017

Folia Histochem Cytobiol.

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Introduction. Prediction of response to preoperative breast cancer chemotherapy may offer a substantial optimization of medical management of this disease. The most efficient prediction would be done a priori, before the start of chemotherapy and based on the biological features of patient and tumor. Numerous markers have been proposed but none of them has been applied as a routine. The role of MKI67 and HSP90 expression has been recently suggested to predict treatment sensitivity in HER2-positive breast cancer. The aim of this study was to validate the utility of proliferation based markers (MKI67 and CDK1) and heat shock proteins (namely HSP90) to predict response to chemotherapy in cohort of breast cancer patients treated preoperatively. Material and methods. Ninety-three patients with breast cancer, all females, mean age 42.2 years, among them 32% T1-T2 patients, 49% T3 patients and 13% with T4 tumor stage, 27% N0, 42% N1, 16% N2, 15% N3 were subjected to initial chemotherapy. The majority of patients (86%) received anthracycline and taxane chemotherapy. Among the patients there were 9 individuals with metastatic disease (M1) at initial presentation, and 11 patients were not treated surgically after initial chemotherapy (no sufficient disease response). From 82 patients operated on, 20 patients (24%) showed pathological complete response (pCR), while in 62 patients there was Results. There were no statistically significant differences in MKI67 and CDK1 expression between pCR and no pCR groups (p = 0.099 and 0.35, respectively), although the median expression of both genes was slightly higher in pCR group. In contrast, both HSP90AA1 and HSP90AB1 transcripts showed decreased expression in pCR group (medians 0.77 and 0.55) when compared to no pCR group (median 0.86 and 0.73), statistically significant for HSP90AA1 (p = 0.031) and of borderline significance for HSP90AB1 (p = 0.054). The most significant predictor of pCR was the ratio of CDK1 transcript to HSP90AA transcript. This ratio was significantly higher in CR group (median 0.99) than in no CR group (median 0.68, p = 0.0023), and showed a potential diagnostic utility (area under receiver operating characteristic [ROC] curve 0.72). Conclusions. HSP90AA1 and AB1 genes exhibit low expression in breast cancers highly sensitive to chemotherapy and may indicate the patients with higher probability of pathological complete response. The ratio of HSP90AA1 to proliferation-related markers (CDK1 or MKI67) may be even better predictor of pCR chance, with higher expression of proliferation genes and lower stress response in patients sensitive to chemotherapy.

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“…Many studies have been performed to prove the accuracy of this new strategy and "a new HSP target". Recent studies showed that HSP inhibition by using antisense oligonucleotides or inhibitors has revealed successful results in clinical trials related to cancer treatment [25][26][27][28][29][30]. Besides, several plant extracts and some natural compounds have been used to suppress HSP expression in cancer cells for a long time [31][32][33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Heat Shock Proteins and Cancer: Plant Based Therapy

Uçar

2015

Heat Shock Proteins

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Cancer is one of the major causes of mortality in the world. Each year approximately 13 million people suffer from cancer disease, and approximately 60 % of them die because of cancer. Besides most of the patients response harmful side effects of chemo-and radiotherapies. Therefore the establishment of new therapeutic strategies for the treatment of cancers will be required. A number of studies have shown that some HSP are induced in specific tumor cells. For example, increased levels of HSP105, HSP90, HSP70, HSP60, HSP27 have been detected in colon cancer, lung cancer, hepatocellular carcinoma, colorectal cancer, and gliomas, respectively. Elevated HSP levels in tumor cells are suggested to be responsible for increased chemotherapy resistance and poor prognosis. Suppression of HSP expressions in cancer cells is a new strategy for the treatment. It is well known that some plant extracts and their flavonoids significantly decrease HSP expression, and induce apoptosis of cancer cells. In addition, using of the HSP inhibitors in association with classical chemotherapy increases the sensitivity of cancer cells to the cytotoxic drugs. Therefore, some plants and their biologically active natural compounds have been investigated for their possible contribution to cancer therapy. The current chapter reviews the role of HSP in different cancer types and suppressing HSP with some natural products.

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Heat Shock Protein as Molecular Targets for Breast Cancer Therapeutics

Cited by 54 publications

References 81 publications

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

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

Ratio of proliferation markers and HSP90 gene expression as a predictor of pathological complete response in breast cancer neoadjuvant chemotherapy

Heat Shock Proteins and Cancer: Plant Based Therapy

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