Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell Lines
Recurrence of ovarian cancer (OvCa) following surgery and standard carboplatin/paclitaxel first-line therapy signifies poor median progression-free survival (<24 months) in the majority of patients with OvCa. The current study utilized unbiased high-throughput screening (HTS) to evaluate an FDA-a...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/12/598 |
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| author | Haya Albanna Alesia Gjoni Danielle Robinette Gerardo Rodriguez Lora Djambov Margaret E. Olson Peter C. Hart |
| author_facet | Haya Albanna Alesia Gjoni Danielle Robinette Gerardo Rodriguez Lora Djambov Margaret E. Olson Peter C. Hart |
| author_sort | Haya Albanna |
| collection | DOAJ |
| description | Recurrence of ovarian cancer (OvCa) following surgery and standard carboplatin/paclitaxel first-line therapy signifies poor median progression-free survival (<24 months) in the majority of patients with OvCa. The current study utilized unbiased high-throughput screening (HTS) to evaluate an FDA-approved compound library for drugs that could be repurposed to improve OvCa sensitivity to carboplatin. The initial screen revealed six compounds with agonistic activity for the adrenoceptor alpha-2a (ADRA2A). These findings were validated in multiple OvCa cell lines (TYKnu, CAOV3, OVCAR8) using three ADRA2A agonists (xylazine, dexmedetomidine, and clonidine) and two independent viability assays. In all the experiments, these compounds enhanced the cytotoxicity of carboplatin treatment. Genetic overexpression of ADRA2A was also sufficient to reduce cell viability and increase carboplatin sensitivity. Taken together, these data indicate that ADRA2A activation may promote chemosensitivity in OvCa, which could be targeted by widely used medications currently indicated for other disease states. |
| first_indexed | 2024-03-08T20:53:45Z |
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| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-08T20:53:45Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-77a099205d9846229380b9b5746461a82023-12-22T14:00:37ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-11-0145129566957810.3390/cimb45120598Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell LinesHaya Albanna0Alesia Gjoni1Danielle Robinette2Gerardo Rodriguez3Lora Djambov4Margaret E. Olson5Peter C. Hart6College of Science, Health and Pharmacy, Roosevelt University, 1400 N Roosevelt Blvd, Schaumburg, IL 60173, USACollege of Science, Health and Pharmacy, Roosevelt University, 1400 N Roosevelt Blvd, Schaumburg, IL 60173, USACollege of Science, Health and Pharmacy, Roosevelt University, 1400 N Roosevelt Blvd, Schaumburg, IL 60173, USACollege of Science, Health and Pharmacy, Roosevelt University, 1400 N Roosevelt Blvd, Schaumburg, IL 60173, USACollege of Science, Health and Pharmacy, Roosevelt University, 1400 N Roosevelt Blvd, Schaumburg, IL 60173, USACollege of Science, Health and Pharmacy, Roosevelt University, 1400 N Roosevelt Blvd, Schaumburg, IL 60173, USACollege of Science, Health and Pharmacy, Roosevelt University, 1400 N Roosevelt Blvd, Schaumburg, IL 60173, USARecurrence of ovarian cancer (OvCa) following surgery and standard carboplatin/paclitaxel first-line therapy signifies poor median progression-free survival (<24 months) in the majority of patients with OvCa. The current study utilized unbiased high-throughput screening (HTS) to evaluate an FDA-approved compound library for drugs that could be repurposed to improve OvCa sensitivity to carboplatin. The initial screen revealed six compounds with agonistic activity for the adrenoceptor alpha-2a (ADRA2A). These findings were validated in multiple OvCa cell lines (TYKnu, CAOV3, OVCAR8) using three ADRA2A agonists (xylazine, dexmedetomidine, and clonidine) and two independent viability assays. In all the experiments, these compounds enhanced the cytotoxicity of carboplatin treatment. Genetic overexpression of ADRA2A was also sufficient to reduce cell viability and increase carboplatin sensitivity. Taken together, these data indicate that ADRA2A activation may promote chemosensitivity in OvCa, which could be targeted by widely used medications currently indicated for other disease states.https://www.mdpi.com/1467-3045/45/12/598ovarian cancerOvCacarboplatin resistanceADRA2Aadrenoceptor alpha-2a |
| spellingShingle | Haya Albanna Alesia Gjoni Danielle Robinette Gerardo Rodriguez Lora Djambov Margaret E. Olson Peter C. Hart Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell Lines Current Issues in Molecular Biology ovarian cancer OvCa carboplatin resistance ADRA2A adrenoceptor alpha-2a |
| title | Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell Lines |
| title_full | Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell Lines |
| title_fullStr | Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell Lines |
| title_full_unstemmed | Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell Lines |
| title_short | Activation of Adrenoceptor Alpha-2 (ADRA2A) Promotes Chemosensitization to Carboplatin in Ovarian Cancer Cell Lines |
| title_sort | activation of adrenoceptor alpha 2 adra2a promotes chemosensitization to carboplatin in ovarian cancer cell lines |
| topic | ovarian cancer OvCa carboplatin resistance ADRA2A adrenoceptor alpha-2a |
| url | https://www.mdpi.com/1467-3045/45/12/598 |
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