Alsevirone-NF Reduces Serum Testosterone and Inhibits Prostate Cancer Xenograft Growth in Balb/c Nude Mice
| Autor: | Galina B. Smirnova, Yulia A. Borisova, R.L.M. Almanza, Vasiliy A. Kudinov, Alexandra S. Latysheva, K. K. Baskaev, Olga Yu Alekseeva, Natalia Yu. Anisimova, Olga M. Ipatova, Vladimir A. Zolottsev, Vadim S. Pokrovsky |
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| Rok vydání: | 2020 |
| Předmět: |
Serum testosterone
0303 health sciences Cancer Research biology business.industry medicine.disease biology.organism_classification BALB/c 03 medical and health sciences Prostate cancer 0302 clinical medicine Oncology 030220 oncology & carcinogenesis Cancer research medicine General Pharmacology Toxicology and Pharmaceutics business 030304 developmental biology |
| Zdroj: | Clinical Cancer Drugs. 7:113-118 |
| ISSN: | 2212-697X |
| Popis: | Background: The goal of this study was to evaluate the anticancer and testosteroneinhibitory effects of 2‘-[(E) androst-5-en-17-ylidene]methyl-4‘,5‘-dihydro-1‘,3‘-oxazole-3β-oleate (Alsevirone-NF). Materials and Methods: PC-3, DU-145, LnCap and 22rv1 prostate cancer cell lines were used for MTT assay. 22rv1 subcutaneous cancer xenografts in Balb/c nude mice were used for in vivo efficacy experiments. Testosterone level was determined after repeated administration of Abiraterone 20, 100 or 200 mg/kg vs Alsevirone-NF 5, 25 or 50 mg/kg daily for 14 days. Results: Alsevirone-NF induced more significant cytotoxicity against PC3, 22rv1 and DU-145 cell lines compared to Abiraterone or Alsevirone-treated control: IC50 7.1 vs 20.6 vs 29.1 μg/ml, 7.7 vs 20.0 vs 12.7 μg/ml, 3.8 vs 43.4 vs 8.5 μg/ml, respectively. IC50 in LnCap cells was almost equal for all three studied agents, 29.2 vs 26.2 vs 30.2 μg/ml for Abiraterone, Alsevirone and Alsevirone-NF. In gonadectomized mice, significant reduction of testosterone level was observed in mice receiving Alsevirone-NF in a maximum single dose of 50 mg/kg (cumulative dose 700 mg/kg): 0.2 nmol/l vs 0.57 nmol/l in control group and 0.83 nmol/l in Abiraterone group, single dose 100 mg/kg. Statistically significant anticancer effect in vivo was obtained on day 11 after the start of treatment: Abiraterone T/C = 27% (p Conclusion: Alsevirone-NF exhibited higher cytotoxic activity, comparable anticancer effect in 22rv1-bearing Balb/c nude mice and provided a more significant reduction of testosterone level in gonadectomized mice in direct comparison against Abiraterone. |
| Databáze: | OpenAIRE |
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