Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells
Introduction. Chemotherapy with Cabazitaxel (CBZ) is a typical first-line treatment option for naïive castration-resistant prostate cancer resistant to docetaxel. On the other hand, Cabazitaxel's therapeutic success is constrained by chemoresistance and side effects.Aim. To assess whether 6 alp...
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LLC Center of Pharmaceutical Analytics (LLC «CPHA»)
2023-02-01
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| Series: | Разработка и регистрация лекарственных средств |
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| Online Access: | https://www.pharmjournal.ru/jour/article/view/1435 |
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| author | M. H. Zalzala W. S. Al-khfajy R. A. Khaleel |
| author_facet | M. H. Zalzala W. S. Al-khfajy R. A. Khaleel |
| author_sort | M. H. Zalzala |
| collection | DOAJ |
| description | Introduction. Chemotherapy with Cabazitaxel (CBZ) is a typical first-line treatment option for naïive castration-resistant prostate cancer resistant to docetaxel. On the other hand, Cabazitaxel's therapeutic success is constrained by chemoresistance and side effects.Aim. To assess whether 6 alpha-ethylchenodeoxycholic acid (6-ECDCA), a selective agonist for bile acid receptors will enhance the efficacy of CBZ in androgen-independent prostate cancer cells.Materials and methods. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay was used to assess the cytotoxicity of 6-ECDCA and CBZ medicines or their combinations against the human prostate cancer cell line (PC-3). The combination outcome suggested by Chou TC et al. was then evaluated using the combination index (CI) to find out the nature of synergism, antagonism, and additive effect of the drug’s combination. Furthermore, the Dose-Reduction Index (DRI) was determined to measure how many times the dose could be reduced for each drug in a synergistic combination.Results and discussion. Analysis of the dose-effect curve showed that the treatment of PC-3 cells with CBZ alone or combined with 6-ECDCA for 48 h led to 50 % cytotoxicity of 20.5 nM and 4.7 nM, respectively. 6-ECDCA at 1.77 µM had an additive effect based on the CI value, which was 1.02, while at 21.02 µM, the CI was 0.54 which designates a strong synergistic effect. The combination of CBZ and 6-ECDCA at a submaximal lower dose by 6-folds of each one produced a 95 % cell death than treatment with either agent alone.Conclusion. The Combination index plot showed CI ≤ l for all combinations used in this study, which indicates additive and synergistic interactions between CBZ and 6-ECDCA. The significant impact of 6-ECDCA in combination with CBZ for treating androgen-independent prostate cancer cells was confirmed by this study to be preferred to the treatment with a single drug. |
| format | Article |
| id | doaj-art-b9acef89b445487d92c4a2df204e3f78 |
| institution | DOAJ |
| issn | 2305-2066 2658-5049 |
| language | Russian |
| publishDate | 2023-02-01 |
| publisher | LLC Center of Pharmaceutical Analytics (LLC «CPHA») |
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| series | Разработка и регистрация лекарственных средств |
| spelling | doaj-art-b9acef89b445487d92c4a2df204e3f782025-08-20T03:19:32ZrusLLC Center of Pharmaceutical Analytics (LLC «CPHA»)Разработка и регистрация лекарственных средств2305-20662658-50492023-02-01121525810.33380/2305-2066-2023-12-1-52-581072Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 CellsM. H. Zalzala0W. S. Al-khfajy1R. A. Khaleel2Department of Pharmacology and Toxicology, University of Baghdad, College of PharmacyDepartment of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah UniversityDepartment of Pharmacology, College of Medicine, University of Al IraqiaIntroduction. Chemotherapy with Cabazitaxel (CBZ) is a typical first-line treatment option for naïive castration-resistant prostate cancer resistant to docetaxel. On the other hand, Cabazitaxel's therapeutic success is constrained by chemoresistance and side effects.Aim. To assess whether 6 alpha-ethylchenodeoxycholic acid (6-ECDCA), a selective agonist for bile acid receptors will enhance the efficacy of CBZ in androgen-independent prostate cancer cells.Materials and methods. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay was used to assess the cytotoxicity of 6-ECDCA and CBZ medicines or their combinations against the human prostate cancer cell line (PC-3). The combination outcome suggested by Chou TC et al. was then evaluated using the combination index (CI) to find out the nature of synergism, antagonism, and additive effect of the drug’s combination. Furthermore, the Dose-Reduction Index (DRI) was determined to measure how many times the dose could be reduced for each drug in a synergistic combination.Results and discussion. Analysis of the dose-effect curve showed that the treatment of PC-3 cells with CBZ alone or combined with 6-ECDCA for 48 h led to 50 % cytotoxicity of 20.5 nM and 4.7 nM, respectively. 6-ECDCA at 1.77 µM had an additive effect based on the CI value, which was 1.02, while at 21.02 µM, the CI was 0.54 which designates a strong synergistic effect. The combination of CBZ and 6-ECDCA at a submaximal lower dose by 6-folds of each one produced a 95 % cell death than treatment with either agent alone.Conclusion. The Combination index plot showed CI ≤ l for all combinations used in this study, which indicates additive and synergistic interactions between CBZ and 6-ECDCA. The significant impact of 6-ECDCA in combination with CBZ for treating androgen-independent prostate cancer cells was confirmed by this study to be preferred to the treatment with a single drug.https://www.pharmjournal.ru/jour/article/view/14356 alpha-ethylchenodeoxycholic acidcabazitaxelsynergistic combination chemotherapy |
| spellingShingle | M. H. Zalzala W. S. Al-khfajy R. A. Khaleel Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells Разработка и регистрация лекарственных средств 6 alpha-ethylchenodeoxycholic acid cabazitaxel synergistic combination chemotherapy |
| title | Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells |
| title_full | Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells |
| title_fullStr | Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells |
| title_full_unstemmed | Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells |
| title_short | Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells |
| title_sort | cytotoxic effect of 6 ethyl chenodeoxycholic acid and cabazitaxel on pc 3 cells |
| topic | 6 alpha-ethylchenodeoxycholic acid cabazitaxel synergistic combination chemotherapy |
| url | https://www.pharmjournal.ru/jour/article/view/1435 |
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