Interaction of Adenosine, Modified Using Carborane Clusters, with Ovarian Cancer Cells: A New Anticancer Approach against Chemoresistance
Platinum compounds remain the first-line drugs for the treatment of most lethal gynecological malignancies and ovarian cancers. Acquired platinum resistance remains a major challenge in gynecological oncology. Considering the unique physicochemical properties of the metallacarboranes modifier and th...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/15/3855 |
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| author | Katarzyna Bednarska-Szczepaniak Ewelina Przelazły Katarzyna Dominika Kania Marzena Szwed Miroslava Litecká Bohumír Grűner Zbigniew J. Leśnikowski |
| author_facet | Katarzyna Bednarska-Szczepaniak Ewelina Przelazły Katarzyna Dominika Kania Marzena Szwed Miroslava Litecká Bohumír Grűner Zbigniew J. Leśnikowski |
| author_sort | Katarzyna Bednarska-Szczepaniak |
| collection | DOAJ |
| description | Platinum compounds remain the first-line drugs for the treatment of most lethal gynecological malignancies and ovarian cancers. Acquired platinum resistance remains a major challenge in gynecological oncology. Considering the unique physicochemical properties of the metallacarboranes modifier and the significant role of nucleoside derivatives as anticancer antimetabolites, we designed and synthesized a set of adenosine conjugates with metallacarboranes containing iron, cobalt, or chromium as semi-abiotic compounds that influence the cisplatin sensitivity of ovarian cancer cells. Adherent cultures of ovarian carcinoma cell lines and multicellular spheroids, ranging from sensitive to highly resistant including experimental cell lines “not responding” to platinum drugs were used. Iron-containing metallacarborane conjugates showed the best anticancer activity, especially against resistant cells. Compound modified at the C2′ nucleoside position showed the best activity in resistant cancer cells and highly resistant cancer spheroids exposed to cisplatin, increasing cell cycle arrest, apoptosis or necrosis, and reactive oxygen species production. Moreover, it showed high cellular accumulation and did not induce cross-resistance to cisplatin, carboplatin, doxorubicin, paclitaxel, or gemcitabine in long-term cultures. The reference <i>nido</i>-carborane derivative (no metal ions) and unmodified nucleosides were not as effective. These findings indicate that metallacarborane modification of adenosine may sensitize ovarian cancer cells to cisplatin in combination treatment. |
| first_indexed | 2024-03-10T09:18:25Z |
| format | Article |
| id | doaj.art-f6ca1cd8c2884a11807f25cc4d3d0cf5 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:18:25Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f6ca1cd8c2884a11807f25cc4d3d0cf52023-11-22T05:28:58ZengMDPI AGCancers2072-66942021-07-011315385510.3390/cancers13153855Interaction of Adenosine, Modified Using Carborane Clusters, with Ovarian Cancer Cells: A New Anticancer Approach against ChemoresistanceKatarzyna Bednarska-Szczepaniak0Ewelina Przelazły1Katarzyna Dominika Kania2Marzena Szwed3Miroslava Litecká4Bohumír Grűner5Zbigniew J. Leśnikowski6Laboratory of Medicinal Chemistry, Polish Academy of Sciences, Institute of Medical Biology, 106 Lodowa, 92-232 Lodz, PolandLaboratory of Medicinal Chemistry, Polish Academy of Sciences, Institute of Medical Biology, 106 Lodowa, 92-232 Lodz, PolandLaboratory of Transcriptional Regulation, Polish Academy of Sciences, Institute of Medical Biology, 106 Lodowa, 92-232 Lodz, PolandDepartment of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, PolandInstitute of Inorganic Chemistry of the Czech Academy of Sciences, Hlavní 1001, 250 68 Rež, Czech RepublicInstitute of Inorganic Chemistry of the Czech Academy of Sciences, Hlavní 1001, 250 68 Rež, Czech RepublicLaboratory of Medicinal Chemistry, Polish Academy of Sciences, Institute of Medical Biology, 106 Lodowa, 92-232 Lodz, PolandPlatinum compounds remain the first-line drugs for the treatment of most lethal gynecological malignancies and ovarian cancers. Acquired platinum resistance remains a major challenge in gynecological oncology. Considering the unique physicochemical properties of the metallacarboranes modifier and the significant role of nucleoside derivatives as anticancer antimetabolites, we designed and synthesized a set of adenosine conjugates with metallacarboranes containing iron, cobalt, or chromium as semi-abiotic compounds that influence the cisplatin sensitivity of ovarian cancer cells. Adherent cultures of ovarian carcinoma cell lines and multicellular spheroids, ranging from sensitive to highly resistant including experimental cell lines “not responding” to platinum drugs were used. Iron-containing metallacarborane conjugates showed the best anticancer activity, especially against resistant cells. Compound modified at the C2′ nucleoside position showed the best activity in resistant cancer cells and highly resistant cancer spheroids exposed to cisplatin, increasing cell cycle arrest, apoptosis or necrosis, and reactive oxygen species production. Moreover, it showed high cellular accumulation and did not induce cross-resistance to cisplatin, carboplatin, doxorubicin, paclitaxel, or gemcitabine in long-term cultures. The reference <i>nido</i>-carborane derivative (no metal ions) and unmodified nucleosides were not as effective. These findings indicate that metallacarborane modification of adenosine may sensitize ovarian cancer cells to cisplatin in combination treatment.https://www.mdpi.com/2072-6694/13/15/3855ovarian cancerchemoresistancecancer spheroidscisplatinapoptosisreactive oxygen species |
| spellingShingle | Katarzyna Bednarska-Szczepaniak Ewelina Przelazły Katarzyna Dominika Kania Marzena Szwed Miroslava Litecká Bohumír Grűner Zbigniew J. Leśnikowski Interaction of Adenosine, Modified Using Carborane Clusters, with Ovarian Cancer Cells: A New Anticancer Approach against Chemoresistance Cancers ovarian cancer chemoresistance cancer spheroids cisplatin apoptosis reactive oxygen species |
| title | Interaction of Adenosine, Modified Using Carborane Clusters, with Ovarian Cancer Cells: A New Anticancer Approach against Chemoresistance |
| title_full | Interaction of Adenosine, Modified Using Carborane Clusters, with Ovarian Cancer Cells: A New Anticancer Approach against Chemoresistance |
| title_fullStr | Interaction of Adenosine, Modified Using Carborane Clusters, with Ovarian Cancer Cells: A New Anticancer Approach against Chemoresistance |
| title_full_unstemmed | Interaction of Adenosine, Modified Using Carborane Clusters, with Ovarian Cancer Cells: A New Anticancer Approach against Chemoresistance |
| title_short | Interaction of Adenosine, Modified Using Carborane Clusters, with Ovarian Cancer Cells: A New Anticancer Approach against Chemoresistance |
| title_sort | interaction of adenosine modified using carborane clusters with ovarian cancer cells a new anticancer approach against chemoresistance |
| topic | ovarian cancer chemoresistance cancer spheroids cisplatin apoptosis reactive oxygen species |
| url | https://www.mdpi.com/2072-6694/13/15/3855 |
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