Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (<i>Viscum album</i> L.) Extract
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 administrati...
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MDPI AG
2021-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/6/551 |
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| author | Henryk M. Kozłowski Małgorzata Pawlikowska Justyna Sobocińska Tomasz Jędrzejewski Artur Dzialuk Sylwia Wrotek |
| author_facet | Henryk M. Kozłowski Małgorzata Pawlikowska Justyna Sobocińska Tomasz Jędrzejewski Artur Dzialuk Sylwia Wrotek |
| author_sort | Henryk M. Kozłowski |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T10:35:45Z |
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| id | doaj.art-046588d1dd1b4fe7a8a513440338793f |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T10:35:45Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-046588d1dd1b4fe7a8a513440338793f2023-11-21T23:18:25ZengMDPI AGPharmaceuticals1424-82472021-06-0114655110.3390/ph14060551Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (<i>Viscum album</i> L.) ExtractHenryk M. Kozłowski0Małgorzata Pawlikowska1Justyna Sobocińska2Tomasz Jędrzejewski3Artur Dzialuk4Sylwia Wrotek5Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 1 Lwowska Str., 87-100 Torun, PolandDepartment of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 1 Lwowska Str., 87-100 Torun, PolandDepartment of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 1 Lwowska Str., 87-100 Torun, PolandDepartment of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 1 Lwowska Str., 87-100 Torun, PolandDepartment of Genetics, Faculty of Biological Sciences, Kazimierz Wielki University, 10 Powstańców Wielkopolskich Ave., 85-090 Bydgoszcz, PolandDepartment of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 1 Lwowska Str., 87-100 Torun, PolandHeat 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.https://www.mdpi.com/1424-8247/14/6/551mistletoe extracthyperthermiacytokinesfeverinflammationreactive oxygen species |
| spellingShingle | Henryk M. Kozłowski Małgorzata Pawlikowska Justyna Sobocińska Tomasz Jędrzejewski Artur Dzialuk Sylwia Wrotek Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (<i>Viscum album</i> L.) Extract Pharmaceuticals mistletoe extract hyperthermia cytokines fever inflammation reactive oxygen species |
| title | Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (<i>Viscum album</i> L.) Extract |
| title_full | Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (<i>Viscum album</i> L.) Extract |
| title_fullStr | Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (<i>Viscum album</i> L.) Extract |
| title_full_unstemmed | Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (<i>Viscum album</i> L.) Extract |
| title_short | Distinct Modulatory Effects of Fever-Range Hyperthermia on the Response of Breast Cancer Cells and Macrophages to Mistletoe (<i>Viscum album</i> L.) Extract |
| title_sort | distinct modulatory effects of fever range hyperthermia on the response of breast cancer cells and macrophages to mistletoe i viscum album i l extract |
| topic | mistletoe extract hyperthermia cytokines fever inflammation reactive oxygen species |
| url | https://www.mdpi.com/1424-8247/14/6/551 |
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