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Suppression of HSP70 Expression by Quercetin and Its Therapeutic Potential Against Cancer

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HSP70 in Human Diseases and Disorders

Part of the book series: Heat Shock Proteins ((HESP,volume 14))

Abstract

Heat shock response is one of several survival pathways that protects cells against harsh conditions. This response mechanism, which is evolutionarily protected in all organisms, enhances the expression of heat shock proteins (HSP) that show protective properties for cells under stress conditions. High expression of many HSP is observed in cancer, and their functions aides the advancement of disease. It is known that overexpression of HSP70, a member of HSP family, in cancerous cells has been closely associated with tumor cell proliferation, apoptosis inhibition, enhanced migration and metastasis and drug resistance promotion. Therefore, targeting HSP70 in cancer treatment is very important. One of the best-studied inhibitors known for HSP70 is quercetin that is widely distributed flavonoid in the plant kingdom. Several in vivo and in vitro studies have reported the efficacy of quercetin in reducing elevated HSP70 levels in cancer therapy. It has become a focal point as an anticancer agent because of the induction of apoptosis in many different cancer cells. In this chapter, we reviewed the role of HSP70 in different cancer types and the suppressive effect of quercetin on expression of HSP70 family members. Moreover, we emphasized molecular mechanisms targeted by quercetin in cancer and its relationship to Hsp70.

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Abbreviations

Akts (or PKB):

protein kinase B

AMPK:

AMP activated protein kinase

CaMKII:

calcium/calmodulin-dependent protein kinase II

Cdk:

cyclin-dependent kinases

Chk2:

checkpoint kinase 2

CK2:

casein kinase 2

ER:

endoplasmic reticulum

ERK:

extracellular signal-regulated kinase

Hsc:

heat shock cognate

HSE:

heat shock element

HSF:

heat shock factor

HSP:

heat shock protein

IL-6:

interleukin-6

JAK:

Janus kinase

JNK:

C-Jun N-terminal kinase

MAPK:

mitogen-activated protein kinase

MMP:

matrix metalloproteinase

PI3K:

phosphatidylinositol 3-kinase

pRb:

retinoblastoma protein

ROS:

reactive oxygen species

RSK2:

ribosomal protein S6 kinase 2

S6K1:

ribosomal protein S6 kinase beta-1

shRNA:

short hairpin RNA

siRNA:

small interfering RNA

STAT3:

signal transducer and activator of transcription 3

VEGF:

vascular endothelial growth factor

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Acknowledgements

This study was supported by the Research Fund of Istanbul University (Project no. 57959 and 24987).

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Authors and Affiliations

  1. Department of Molecular Biology & Genetics, Faculty of Science, Istanbul University, Istanbul, Turkey

    Evren Önay Uçar, Aslıhan Şengelen, Elif Mertoğlu, Murat Pekmez & Nazlı Arda

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  1. Evren Önay Uçar
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  2. Aslıhan Şengelen
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Correspondence to Evren Önay Uçar .

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  1. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Punit Kaur

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Önay Uçar, E., Şengelen, A., Mertoğlu, E., Pekmez, M., Arda, N. (2018). Suppression of HSP70 Expression by Quercetin and Its Therapeutic Potential Against Cancer. In: Asea, A., Kaur, P. (eds) HSP70 in Human Diseases and Disorders. Heat Shock Proteins, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-89551-2_19

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