Introduction

pharmjournal

Разработка и регистрация лекарственных средств

Drug development & registration

2305-20662658-5049

LLC «CPHA»

10.33380/2305-2066-2023-12-1-52-58

pharmjournal-1435

Research Article

ПОИСК И РАЗРАБОТКА НОВЫХ ЛЕКАРСТВЕННЫХ СРЕДСТВ

RESEARCH AND DEVELOPMENT OF NEW DRUG PRODUCTS

Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells

https://orcid.org/0000-0003-0552-6469

Zalzala

M. H.

Zalzala

M. H.

Baghdad-Iraq

https://orcid.org/0000-0003-4451-8939

Al-khfajy

W. S.

Al-khfajy

W. S.

Baghdad-Iraq

pharm.wroodsalim@uomustansiriyah.edu.iq

https://orcid.org/0000-0001-5757-5356

Khaleel

R. A.

Khaleel

R. A.

Baghdad-Iraq

Department of Pharmacology and Toxicology, University of Baghdad, College of PharmacyDepartment of Pharmacology and Toxicology, University of Baghdad, College of Pharmacy

Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University

Department of Pharmacology, College of Medicine, University of Al IraqiaDepartment of Pharmacology, College of Medicine, University of Al Iraqia

2023

27022023

1215258

2023

Zalzala M.H., Al-khfajy W.S., Khaleel R.A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.pharmjournal.ru/jour/article/view/1435

Introduction

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

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

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

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

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.

Introduction

Aim

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

Results and discussion

Conclusion

6 alpha-ethylchenodeoxycholic acidCabazitaxelsynergistic combination chemotherapy

The authors thank college of pharmacy / Mustansiriyah University for providing the facilities to perform this study.

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The authors declare that there are no conflicts of interest present.