The Role of Heat Shock Proteins and Autophagy in Mechanisms Underlying Effects of Sulforaphane on Doxorubicin-Induced Toxicity in HEK293 Cells

The Role of Heat Shock Proteins and Autophagy in Mechanisms Underlying Effects of Sulforaphane on Doxorubicin-Induced Toxicity in HEK293 Cells

Doxorubicin (DOX) is a cytostatic agent belonging to anthracycline group. Important role in mechanism associated with negative effects of DOX plays an oxidative stress. Heat shock proteins (HSPs) are part of mechanisms initiated in response to stressful stimuli and play an important role in cellular...

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Bibliographic Details
Published in:Physiological research Vol. 72; no. S1; pp. S47 - S59
Main Authors: Boťanská, B, Pecníková, V, Fogarassyová, M, Barančík, M
Format: Journal Article
Language:English
Published: Czech Republic Institute of Physiology 2023
Institute of Physiology of the Czech Academy of Sciences
Subjects:
Anthracycline
Antibodies
Antioxidants
Apoptosis
Autophagy
Cancer
Cytotoxicity
Doxorubicin
Doxorubicin - toxicity
Enzymes
Free radicals
GA-binding protein
Heat shock proteins
HEK293 Cells
Hsp40 protein
Hsp60 protein
Humans
Kidneys
Oxidation
Oxidative Stress
Sulforaphane
Toxicity
Transcription factors
Up-regulation
United Kingdom > UK
United States > US
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Summary:Doxorubicin (DOX) is a cytostatic agent belonging to anthracycline group. Important role in mechanism associated with negative effects of DOX plays an oxidative stress. Heat shock proteins (HSPs) are part of mechanisms initiated in response to stressful stimuli and play an important role in cellular responses to oxidative stress through interaction with components of redox signaling. The present work was aimed to study the role of HSPs and autophagy in mechanisms underlying effects of sulforaphane (SFN), a potential activator of Nrf-2, on doxorubicin-induced toxicity in human kidney HEK293 cells. We investigated effects of SFN and DOX on proteins associated with regulation of heat shock response, redox signaling, and autophagy. Results show that SFN significantly reduced cytotoxic effects of DOX. The positive effects of SFN on DOX-induced changes were associated with up-regulation of Nrf-2 and HSP60 protein levels. In the case of another heat shock protein HSP40, SFN increased its levels when was administered alone but not in conditions when cells were exposed to the effects of DOX. Sulforaphane also reversed negative effects of DOX on activities of superoxide dismutases (SODs) and up-regulation of autophagy markers (LC3A/B-II, Atg5, and Atg12). In conclusion, the changes observed in HSP60 are of particular importance in terms of protecting cells from the effects of DOX. Finding that under conditions where SFN reduced cytotoxic effects of DOX were significantly increased protein levels of both Nrf-2 and HSP60 point to the role of HSP60 in mechanisms of redox signaling underlying effects of SFN on DOX-induced toxicity in HEK293 cells. Moreover, data confirmed an important role of autophagy in effects of SFN on DOX-induced toxicity.
ISSN:0862-8408
1802-9973
DOI:10.33549/physiolres.935107