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Article

Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (Viscum album L.) Extract

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Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 1 Lwowska Str., 87-100 Torun, Poland
2
Department of Genetics, Faculty of Biological Sciences, Kazimierz Wielki University, 10 Powstańców Wielkopolskich Ave., 85-090 Bydgoszcz, Poland
*
Authors to whom correspondence should be addressed.
Academic Editor: Jan-Pieter Konsman
Pharmaceuticals 2021, 14(6), 551; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060551
Received: 5 May 2021 / Revised: 3 June 2021 / Accepted: 6 June 2021 / Published: 8 June 2021
(This article belongs to the Special Issue Cerebral Production and Action of Pro-inflammatory Cytokines)
Heat utility as a critical component of fever is often ignored, although the symptom is observed in many medical conditions. Mistletoe extract (ME) is an adjunctive medication prescribed to cancer patients. The increase in body temperature is frequently observed in patients following ME administration. Nevertheless, the impact of this fever on the effectiveness of therapy is unknown. Therefore, we aimed to investigate the effect of fever-range temperatures on ME-treated breast cancer cells and macrophages. The cells were simultaneously stimulated with ME and subjected to fever-range hyperthermia (FRH; 39 °C or 41 °C). After co-treatment, the cell viability, generation of reactive oxygen species (ROS), cell cycle distribution, and production of pro-inflammatory factors (interleukin (IL)-1β, IL-6, and cyclooxygenase (COX)-2) were evaluated. The results showed that the exposure of ME-treated breast cancer cells to FRH at 39 °C resulted in a slight decrease in their viability, whereas FRH of 41 °C enhanced this effect. Only FRH of 41 °C induced minor changes in ROS level in ME-treated breast cancer cell lines. In ME-treated macrophages, FRH stimulated cell proliferation. The cell cycle distribution analysis showed a difference between cells cultured at 39 °C and 41 °C in all examined cell lines. Moreover, hyperthermia at 41 °C completely inhibited the ME-induced increase in IL-1β and IL-6 expression in MCF-7 breast cancer cells, whereas this effect was not observed in 4T1 breast cancer cells. In contrast, in ME-treated macrophages, FRH of 41 °C strongly up-regulated expression of the pro-inflammatory factors. We conclude that fever is an important component of ME therapy that differentially affects cancer and immune cells. View Full-Text
Keywords: mistletoe extract; hyperthermia; cytokines; fever; inflammation; reactive oxygen species; cell cycle distribution mistletoe extract; hyperthermia; cytokines; fever; inflammation; reactive oxygen species; cell cycle distribution
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MDPI and ACS Style

Kozłowski, H.M.; Pawlikowska, M.; Sobocińska, J.; Jędrzejewski, T.; Dzialuk, A.; Wrotek, S. Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (Viscum album L.) Extract. Pharmaceuticals 2021, 14, 551. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060551

AMA Style

Kozłowski HM, Pawlikowska M, Sobocińska J, Jędrzejewski T, Dzialuk A, Wrotek S. Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (Viscum album L.) Extract. Pharmaceuticals. 2021; 14(6):551. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060551

Chicago/Turabian Style

Kozłowski, Henryk M., Małgorzata Pawlikowska, Justyna Sobocińska, Tomasz Jędrzejewski, Artur Dzialuk, and Sylwia Wrotek. 2021. "Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (Viscum album L.) Extract" Pharmaceuticals 14, no. 6: 551. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060551

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