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Targeting of Heat Shock Proteins by Natural Products in Cancer

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Molecular Oncology: Underlying Mechanisms and Translational Advancements

Abstract

Initially discovered as a group of proteins showing significantly higher expression in response to heat stress, Heat shock proteins (HSPs) have gained considerable appreciation. Overwhelmingly increasing scientific evidence has highlighted the role of these proteins as molecular chaperones which trigger protein holding and folding thus facilitating freshly synthesized protein/s to achieve mature and biologically active conformation. It is becoming progressively more understandable that HSPs are involved in post-translational modification of proteins of signaling cascades, modulation of apoptosis related proteins, assembly and disassembly of transcriptional machinery. Recently emerging functional and structural data has provided new insights related to biochemical regulation of HSPs and the structural dynamics used by these proteins to act on a diverse client repertoire.

Different strategies are currently being tested to effectively inhibit/downregulate HSPs in cancer cells. Wide ranging natural products, particularly, antioxidant compounds, prevent HSP expression and induce apoptosis in tumor cells. Besides, these compounds help to reduce off-target effects of radio- or chemotherapies in many types of cancers.

Plethora of information has considerably improved our understanding of the molecular and cellular basis of HSP induced regulation of myriad of proteins and these insights may lead to the development of efficient therapeutic agents. The current chapter focuses on suppression of HSPs by using natural compounds in cancer cells.

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Abbreviations

17-AAG:

17-allylamino-17-demethoxygeldanamycin

7-KC:

7-Ketocholestrol

ALS:

Amyotrophic lateral sclerosis

CDDP:

Cisplatin

CML:

Chronic myelogenous leukemia

DMC:

Demethoxycurcumin

Dox:

Doxorubicin

EGCG:

Epigallocatechin-3-gallate

HSF:

Heat shock factor

HSP:

Heat shock protein

HSR:

Heat shock response

PEITC:

Phenethyl isothiocyanate

siRNA:

Small interfering RNA

TF:

Theaflavin

TR:

Thearubigin

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Acknowledgements

The authors wish to dedicate this chapter to the memory of Professor Alastair Aitken for his invaluable motivation and great contribution to their knowledge and experience, both in science and in life. The authors also thank to Michele Learmonth and Gökçe Ünar for helpful suggestions. This study was supported by the Research Fund of Istanbul University (Project no. T-746/13092005, 22649 and 27484).

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

    Evren Önay Uçar, Murat Pekmez & Nazlı Arda

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  1. Evren Önay Uçar
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  2. Murat Pekmez
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Correspondence to Evren Önay Uçar .

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  1. Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan

    Ammad Ahmad Farooqi

  2. Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan

    Muhammad Ismail

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Önay Uçar, E., Pekmez, M., Arda, N. (2017). Targeting of Heat Shock Proteins by Natural Products in Cancer. In: Farooqi, A., Ismail, M. (eds) Molecular Oncology: Underlying Mechanisms and Translational Advancements. Springer, Cham. https://doi.org/10.1007/978-3-319-53082-6_8

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