Exploring adenosine analogs for chondrosarcoma therapy: In vitro and in vivo insights
Chondrosarcomas (CSs) are resistant to conventional chemotherapy and radiotherapy. Therefore, new therapeutic approaches are needed. The aim of this study was to validate the use of adenosine analogs as a new therapeutic strategy for the treatment of CS. Five adenosine analogs (aristeromycin, cladri...
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Elsevier
2025-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253125001969 |
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| author | Marion Lenté Juliette Aury-Landas Mahdia Taieb Benoît Bernay Eva Lhuissier Karim Boumédiene Catherine Baugé |
| author_facet | Marion Lenté Juliette Aury-Landas Mahdia Taieb Benoît Bernay Eva Lhuissier Karim Boumédiene Catherine Baugé |
| author_sort | Marion Lenté |
| collection | DOAJ |
| description | Chondrosarcomas (CSs) are resistant to conventional chemotherapy and radiotherapy. Therefore, new therapeutic approaches are needed. The aim of this study was to validate the use of adenosine analogs as a new therapeutic strategy for the treatment of CS. Five adenosine analogs (aristeromycin, cladribine, clofarabine, formycin, and pentostatin) were evaluated in vitro on CS cell lines via both (two-dimensional) 2D cultures and three-dimensional (3D) alginate bead models. Cell viability was assessed by cell counting or ATP assays. Apoptosis was measured and cell cycle analyzed. The most promising compounds were further tested in vivo using a xenograft CS model in nude mice. Four analogs significantly reduced the viability of CSs. Among these, cladribine and clofarabine demonstrated potent efficacy in both 2D and 3D models by inducing apoptosis. Cladribine was further found to induce cell-cycle arrest, leading to apoptosis-mediated cell death. In vivo, both cladribine and clofarabine exhibited substantial antitumor effects in a xenograft model. In conclusion, cladribine and clofarabine, which have already been approved for clinical use in leukemia and multiple sclerosis, are promising candidates for the treatment of CS. Their efficacy in preclinical models suggests that these molecules could be repurposed for phase 2 clinical trials in patients with CS. |
| format | Article |
| id | doaj-art-cb098cb56bd84d9394df718c8b0bc78b |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-cb098cb56bd84d9394df718c8b0bc78b2025-08-20T04:00:32ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-09-0136310264210.1016/j.omtn.2025.102642Exploring adenosine analogs for chondrosarcoma therapy: In vitro and in vivo insightsMarion Lenté0Juliette Aury-Landas1Mahdia Taieb2Benoît Bernay3Eva Lhuissier4Karim Boumédiene5Catherine Baugé6Université de Caen Normandie, UR7451 BioConnect, 14000 Caen, FranceUniversité de Caen Normandie, UR7451 BioConnect, 14000 Caen, France; Université de Caen Normandie, CNRS, Normandie Université, GIP CYCERON, UMR6030 ISTCT, 14000 Caen, FranceUniversité de Caen Normandie, UR7451 BioConnect, 14000 Caen, FranceUniversité de Caen Normandie, US Emerode, PROTEOGEN, 14000 Caen, FranceUniversité de Caen Normandie, UR7451 BioConnect, 14000 Caen, FranceUniversité de Caen Normandie, UR7451 BioConnect, 14000 Caen, FranceUniversité de Caen Normandie, UR7451 BioConnect, 14000 Caen, France; Corresponding author: Catherine Baugé, Université de Caen Normandie, UR7451 BioConnect, 14000 Caen, France.Chondrosarcomas (CSs) are resistant to conventional chemotherapy and radiotherapy. Therefore, new therapeutic approaches are needed. The aim of this study was to validate the use of adenosine analogs as a new therapeutic strategy for the treatment of CS. Five adenosine analogs (aristeromycin, cladribine, clofarabine, formycin, and pentostatin) were evaluated in vitro on CS cell lines via both (two-dimensional) 2D cultures and three-dimensional (3D) alginate bead models. Cell viability was assessed by cell counting or ATP assays. Apoptosis was measured and cell cycle analyzed. The most promising compounds were further tested in vivo using a xenograft CS model in nude mice. Four analogs significantly reduced the viability of CSs. Among these, cladribine and clofarabine demonstrated potent efficacy in both 2D and 3D models by inducing apoptosis. Cladribine was further found to induce cell-cycle arrest, leading to apoptosis-mediated cell death. In vivo, both cladribine and clofarabine exhibited substantial antitumor effects in a xenograft model. In conclusion, cladribine and clofarabine, which have already been approved for clinical use in leukemia and multiple sclerosis, are promising candidates for the treatment of CS. Their efficacy in preclinical models suggests that these molecules could be repurposed for phase 2 clinical trials in patients with CS.http://www.sciencedirect.com/science/article/pii/S2162253125001969MT: Oligonucleotides: Therapies and Applicationsadenosine analogscladribineclofarabinechondrosarcomaapoptosis |
| spellingShingle | Marion Lenté Juliette Aury-Landas Mahdia Taieb Benoît Bernay Eva Lhuissier Karim Boumédiene Catherine Baugé Exploring adenosine analogs for chondrosarcoma therapy: In vitro and in vivo insights Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications adenosine analogs cladribine clofarabine chondrosarcoma apoptosis |
| title | Exploring adenosine analogs for chondrosarcoma therapy: In vitro and in vivo insights |
| title_full | Exploring adenosine analogs for chondrosarcoma therapy: In vitro and in vivo insights |
| title_fullStr | Exploring adenosine analogs for chondrosarcoma therapy: In vitro and in vivo insights |
| title_full_unstemmed | Exploring adenosine analogs for chondrosarcoma therapy: In vitro and in vivo insights |
| title_short | Exploring adenosine analogs for chondrosarcoma therapy: In vitro and in vivo insights |
| title_sort | exploring adenosine analogs for chondrosarcoma therapy in vitro and in vivo insights |
| topic | MT: Oligonucleotides: Therapies and Applications adenosine analogs cladribine clofarabine chondrosarcoma apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2162253125001969 |
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