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Article

Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A

1
Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, 44-102 Gliwice, Poland
2
Division of Medical Biology, Institute of Biology, Jan Kochanowski University, 25-406 Kielce, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Alexander E. Kabakov
Cells 2021, 10(6), 1418; https://doi.org/10.3390/cells10061418
Received: 12 May 2021 / Revised: 2 June 2021 / Accepted: 3 June 2021 / Published: 7 June 2021
Manumycin A (MA) is a well-tolerated natural antibiotic showing pleiotropic anticancer effects in various preclinical in vitro and in vivo models. Anticancer drugs may themselves act as stressors to induce the cellular adaptive mechanism that can minimize their cytotoxicity. Heat shock proteins (HSPs) as cytoprotective factors can counteract the deleterious effects of various stressful stimuli. In this study, we examined whether the anticancer effects of MA can be counteracted by the mechanism related to HSPs belonging to the HSPA (HSP70) family. We found that MA caused cell type-specific alterations in the levels of HSPAs. These changes included concomitant upregulation of the stress-inducible (HSPA1 and HSPA6) and downregulation of the non-stress-inducible (HSPA2) paralogs. However, neither HSPA1 nor HSPA2 were necessary to provide protection against MA in lung cancer cells. Conversely, the simultaneous repression of several HSPA paralogs using pan-HSPA inhibitors (VER-155008 or JG-98) sensitized cancer cells to MA. We also observed that genetic ablation of the heat shock factor 1 (HSF1) transcription factor, a main transactivator of HSPAs expression, sensitized MCF7 cells to MA treatment. Our study reveals that inhibition of HSF1-mediated heat shock response (HSR) can improve the anticancer effect of MA. These observations suggest that targeting the HSR- or HSPA-mediated adaptive mechanisms may be a promising strategy for further preclinical developments. View Full-Text
Keywords: heat shock factor 1; heat shock proteins; HSP70; HSPA1; HSPA2; manumycin A; lung cancer; breast cancer; HSPA inhibitors heat shock factor 1; heat shock proteins; HSP70; HSPA1; HSPA2; manumycin A; lung cancer; breast cancer; HSPA inhibitors
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MDPI and ACS Style

Sojka, D.R.; Hasterok, S.; Vydra, N.; Toma-Jonik, A.; Wieczorek, A.; Gogler-Pigłowska, A.; Scieglinska, D. Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A. Cells 2021, 10, 1418. https://doi.org/10.3390/cells10061418

AMA Style

Sojka DR, Hasterok S, Vydra N, Toma-Jonik A, Wieczorek A, Gogler-Pigłowska A, Scieglinska D. Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A. Cells. 2021; 10(6):1418. https://doi.org/10.3390/cells10061418

Chicago/Turabian Style

Sojka, Damian R., Sylwia Hasterok, Natalia Vydra, Agnieszka Toma-Jonik, Anna Wieczorek, Agnieszka Gogler-Pigłowska, and Dorota Scieglinska. 2021. "Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A" Cells 10, no. 6: 1418. https://doi.org/10.3390/cells10061418

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