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Investigation of the role of quercetin as a heat shock protein inhibitor on apoptosis in human breast cancer cells

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Abstract

High expression of heat shock proteins (Hsp) in breast cancer has been closely associated with tumor cell proliferation and thus a poor clinical outcome. Quercetin, a good Hsp inhibitor as a dietary flavonoid, possesses anticarcinogenic properties. Although there are many studies on the effects of quercetin on Hsp levels in human breast cancer cells, research on elucidation of its molecular mechanism continues. Herein, we aimed to investigate the effect of quercetin on Hsp levels and whether quercetin is a suitable therapeutic for two breast cancer cell lines (MCF-7 and MDA-MB-231) representing breast tumors which differed in hormone receptor, aggressiveness and treatment responses. To examine the response to high and low doses of quercetin, the cells were treated with three doses of quercetin (10, 25 and 100 μM) determined by MTT. The effects of quercetin on Hsp levels, apoptosis and DNA damage were examined by western blot analysis, caspase activity assay, comet assay and microscopy in human breast cancer cells. Compared to MDA-MB231 cells, MCF-7 cells were more affected by quercetin treatments. Quercetin effectively suppressed the expression of Hsp27, Hsp70 and Hsp90. While quercetin did not induce DNA damage, it triggered apoptosis at high levels. Although an increase in NF-κB levels is observed in the cells exposed to quercetin, the net result is the anticancer effect in case of Hsp depletion and apoptosis induction. Taken together our findings suggested that quercetin can be an effective therapeutic agent for breast cancer therapy regardless of the presence or absence of hormone receptors.

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Abbreviations

EMS:

Ethyl methanesulfonate

ER:

Estrogen receptor

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

HER2:

Human epidermal growth factor receptor 2

HSF:

Heat shock factor

Hsp:

Heat shock protein

IC50 :

The half-maximal inhibitory concentration

NF-κB:

Nuclear factor kappa-B

PARP:

Poly (ADP-ribose) polymerase

PR:

Progesterone receptor

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Acknowledgements

This study was funded by The Scientific and Technological Research Council of Turkey (TUBITAK, Grant Number: 1919B011502439), Turkey.

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Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Institute of Graduate Studies in Sciences, Istanbul University, Istanbul, Turkey

    Ezgi Kıyga & Aslıhan Şengelen

  2. Basic Medical Sciences Department of Molecular Biology and Genetics, School of Medicine, Koç University, Istanbul, Turkey

    Zelal Adıgüzel

  3. Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Vezneciler, 34134, Istanbul, Turkey

    Evren Önay Uçar

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  1. Ezgi Kıyga
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Kıyga, E., Şengelen, A., Adıgüzel, Z. et al. Investigation of the role of quercetin as a heat shock protein inhibitor on apoptosis in human breast cancer cells. Mol Biol Rep 47, 4957–4967 (2020). https://doi.org/10.1007/s11033-020-05641-x

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