Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy
Natural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined treatment with cisplatin (CisPt) and Res. We identi...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5715 |
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| author | Agnieszka Synowiec Klaudia Brodaczewska Gabriel Wcisło Aleksandra Majewska Agata Borkowska Aleksandra Filipiak-Duliban Aleksandra Gawrylak Kinga Wilkus Katarzyna Piwocka Agata Kominek Halina Waś Sławomir Lewicki Jacek Siewiera Cezary Szczylik Jolanta Szenajch Jacek Z. Kubiak Claudine Kieda |
| author_facet | Agnieszka Synowiec Klaudia Brodaczewska Gabriel Wcisło Aleksandra Majewska Agata Borkowska Aleksandra Filipiak-Duliban Aleksandra Gawrylak Kinga Wilkus Katarzyna Piwocka Agata Kominek Halina Waś Sławomir Lewicki Jacek Siewiera Cezary Szczylik Jolanta Szenajch Jacek Z. Kubiak Claudine Kieda |
| author_sort | Agnieszka Synowiec |
| collection | DOAJ |
| description | Natural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined treatment with cisplatin (CisPt) and Res. We identified A2780 cells as the most synergistically responding, thus optimal for further analysis. Because hypoxia is the hallmark of the solid tumor microenvironment, we compared the effects of Res alone and in combination with CisPt in hypoxia (pO<sub>2</sub> = 1%) vs. normoxia (pO<sub>2</sub> = 19%). Hypoxia caused an increase (43.2 vs. 5.0%) in apoptosis and necrosis (14.2 vs. 2.5%), reactive oxygen species production, pro-angiogenic HIF-1α (hypoxia-inducible factor-1α) and VEGF (vascular endothelial growth factor), cell migration, and downregulated the expression of ZO1 (zonula occludens-1) protein in comparison to normoxia. Res was not cytotoxic under hypoxia in contrast to normoxia. In normoxia, Res alone or CisPt+Res caused apoptosis via caspase-3 cleavage and BAX, while in hypoxia, it reduced the accumulation of A2780 cells in the G2/M phase. CisPt+Res increased levels of vimentin under normoxia and upregulated SNAI1 expression under hypoxia. Thus, various effects of Res or CisPt+Res on A2780 cells observed in normoxia are eliminated or diminished in hypoxia. These findings indicate the limitations in using Res as an adjuvant with CisPt therapy in OC. |
| first_indexed | 2024-03-11T06:24:43Z |
| format | Article |
| id | doaj.art-15a090ddf72445fb82f11722eb5d22be |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:24:43Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-15a090ddf72445fb82f11722eb5d22be2023-11-17T11:37:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246571510.3390/ijms24065715Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin TherapyAgnieszka Synowiec0Klaudia Brodaczewska1Gabriel Wcisło2Aleksandra Majewska3Agata Borkowska4Aleksandra Filipiak-Duliban5Aleksandra Gawrylak6Kinga Wilkus7Katarzyna Piwocka8Agata Kominek9Halina Waś10Sławomir Lewicki11Jacek Siewiera12Cezary Szczylik13Jolanta Szenajch14Jacek Z. Kubiak15Claudine Kieda16Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandDepartment of Oncology, Centre of Postrgraduate Medical Education, 01-813 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandLaboratory of Cytometry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Cytometry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandInstitute of Outcomes Research, Maria Sklodowska-Curie Medical Academy, 00-136 Warsaw, PolandClinical Department of Hyperbaric Medicine, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandDepartment of Oncology, Centre of Postrgraduate Medical Education, 01-813 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandLaboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, PolandNatural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined treatment with cisplatin (CisPt) and Res. We identified A2780 cells as the most synergistically responding, thus optimal for further analysis. Because hypoxia is the hallmark of the solid tumor microenvironment, we compared the effects of Res alone and in combination with CisPt in hypoxia (pO<sub>2</sub> = 1%) vs. normoxia (pO<sub>2</sub> = 19%). Hypoxia caused an increase (43.2 vs. 5.0%) in apoptosis and necrosis (14.2 vs. 2.5%), reactive oxygen species production, pro-angiogenic HIF-1α (hypoxia-inducible factor-1α) and VEGF (vascular endothelial growth factor), cell migration, and downregulated the expression of ZO1 (zonula occludens-1) protein in comparison to normoxia. Res was not cytotoxic under hypoxia in contrast to normoxia. In normoxia, Res alone or CisPt+Res caused apoptosis via caspase-3 cleavage and BAX, while in hypoxia, it reduced the accumulation of A2780 cells in the G2/M phase. CisPt+Res increased levels of vimentin under normoxia and upregulated SNAI1 expression under hypoxia. Thus, various effects of Res or CisPt+Res on A2780 cells observed in normoxia are eliminated or diminished in hypoxia. These findings indicate the limitations in using Res as an adjuvant with CisPt therapy in OC.https://www.mdpi.com/1422-0067/24/6/5715ovarian cancercisplatinresveratrolnormoxiahypoxiaepithelial–mesenchymal transition markers |
| spellingShingle | Agnieszka Synowiec Klaudia Brodaczewska Gabriel Wcisło Aleksandra Majewska Agata Borkowska Aleksandra Filipiak-Duliban Aleksandra Gawrylak Kinga Wilkus Katarzyna Piwocka Agata Kominek Halina Waś Sławomir Lewicki Jacek Siewiera Cezary Szczylik Jolanta Szenajch Jacek Z. Kubiak Claudine Kieda Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy International Journal of Molecular Sciences ovarian cancer cisplatin resveratrol normoxia hypoxia epithelial–mesenchymal transition markers |
| title | Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy |
| title_full | Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy |
| title_fullStr | Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy |
| title_full_unstemmed | Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy |
| title_short | Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy |
| title_sort | hypoxia but not normoxia reduces effects of resveratrol on cisplatin treatment in a2780 ovarian cancer cells a challenge for resveratrol use in anticancer adjuvant cisplatin therapy |
| topic | ovarian cancer cisplatin resveratrol normoxia hypoxia epithelial–mesenchymal transition markers |
| url | https://www.mdpi.com/1422-0067/24/6/5715 |
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