Antiandrogenic activity and bioavailability of magnolol analogs – A potential for prostate cancer therapeutics
Background: Prostate cancer is the second most common form of cancer in men worldwide and there is a great need for novel treatment strategies, especially for castrate-resistant prostate cancers where the proliferation of the cancer cells is stimulated by androgens produced in the adrenal cortex and...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Phytomedicine Plus |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031323000817 |
| _version_ | 1797627075322970112 |
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| author | Agneta Oskarsson Geeta Mandava Corrado Tringali Luana Pulvirenti Vera Muccilli Johan Lundqvist |
| author_facet | Agneta Oskarsson Geeta Mandava Corrado Tringali Luana Pulvirenti Vera Muccilli Johan Lundqvist |
| author_sort | Agneta Oskarsson |
| collection | DOAJ |
| description | Background: Prostate cancer is the second most common form of cancer in men worldwide and there is a great need for novel treatment strategies, especially for castrate-resistant prostate cancers where the proliferation of the cancer cells is stimulated by androgens produced in the adrenal cortex and the cancer cells. Purpose: In this study, we have investigated the antiandrogenic properties of magnolol and ten synthetic analogs in vitro. Study design and methods: The compounds were evaluated for cytotoxicity, antiandrogenic receptor activity, binding to the androgen receptor, effects on the production of Prostate-specific antigen (PSA), and potential to pass over a tight layer of Caco-2 cells mimicking gastrointestinal absorption. Results: We found that almost all investigated compounds were antiandrogenic in an androgen receptor reporter gene assay, with IC50 values ranging from 7 to 86 µM. Magnolol itself had the highest antiandrogenic potency. Five of the compounds were then evaluated for their binding to the androgen receptor and three of these compounds were found to bind to the receptor. These five compounds were also evaluated for their effect on the PSA production and four were found to decrease PSA production at non-cytotoxic concentrations. The antiandrogenic activity after passage through a layer of Caco-2 cells, mimicking gastrointestinal absorption, was also evaluated for three of the compounds. All three compounds were found to have the capacity to be transported from the apical to the basolateral side of the Caco-2 cell layer and exert antiandrogenic effects after the transport. Conclusion: In conclusion, this study shows that magnolol and analogs have antiandrogenic effects in vitro and that selected analogs can pass over a tight layer of Caco-2 cells, indicating a potential for good bioavailability after oral administration. These magnolol analogs thereby constitute an interesting group of compounds worthy of further evaluation as potential anti-prostate cancer therapeutics. |
| first_indexed | 2024-03-11T10:19:13Z |
| format | Article |
| id | doaj.art-02f900280de94674b2c7c8b47246f529 |
| institution | Directory Open Access Journal |
| issn | 2667-0313 |
| language | English |
| last_indexed | 2024-03-11T10:19:13Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Phytomedicine Plus |
| spelling | doaj.art-02f900280de94674b2c7c8b47246f5292023-11-16T06:11:10ZengElsevierPhytomedicine Plus2667-03132023-11-0134100485Antiandrogenic activity and bioavailability of magnolol analogs – A potential for prostate cancer therapeuticsAgneta Oskarsson0Geeta Mandava1Corrado Tringali2Luana Pulvirenti3Vera Muccilli4Johan Lundqvist5Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, SwedenDepartment of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, SwedenDepartment of Chemical Science, University of Catania, Viale Andrea Doria 6, I-95125 Catania, ItalyDepartment of Chemical Science, University of Catania, Viale Andrea Doria 6, I-95125 Catania, ItalyDepartment of Chemical Science, University of Catania, Viale Andrea Doria 6, I-95125 Catania, ItalyDepartment of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07 Uppsala, Sweden; Corresponding author.Background: Prostate cancer is the second most common form of cancer in men worldwide and there is a great need for novel treatment strategies, especially for castrate-resistant prostate cancers where the proliferation of the cancer cells is stimulated by androgens produced in the adrenal cortex and the cancer cells. Purpose: In this study, we have investigated the antiandrogenic properties of magnolol and ten synthetic analogs in vitro. Study design and methods: The compounds were evaluated for cytotoxicity, antiandrogenic receptor activity, binding to the androgen receptor, effects on the production of Prostate-specific antigen (PSA), and potential to pass over a tight layer of Caco-2 cells mimicking gastrointestinal absorption. Results: We found that almost all investigated compounds were antiandrogenic in an androgen receptor reporter gene assay, with IC50 values ranging from 7 to 86 µM. Magnolol itself had the highest antiandrogenic potency. Five of the compounds were then evaluated for their binding to the androgen receptor and three of these compounds were found to bind to the receptor. These five compounds were also evaluated for their effect on the PSA production and four were found to decrease PSA production at non-cytotoxic concentrations. The antiandrogenic activity after passage through a layer of Caco-2 cells, mimicking gastrointestinal absorption, was also evaluated for three of the compounds. All three compounds were found to have the capacity to be transported from the apical to the basolateral side of the Caco-2 cell layer and exert antiandrogenic effects after the transport. Conclusion: In conclusion, this study shows that magnolol and analogs have antiandrogenic effects in vitro and that selected analogs can pass over a tight layer of Caco-2 cells, indicating a potential for good bioavailability after oral administration. These magnolol analogs thereby constitute an interesting group of compounds worthy of further evaluation as potential anti-prostate cancer therapeutics.http://www.sciencedirect.com/science/article/pii/S2667031323000817MagnololProstateCancerAntiandrogenic |
| spellingShingle | Agneta Oskarsson Geeta Mandava Corrado Tringali Luana Pulvirenti Vera Muccilli Johan Lundqvist Antiandrogenic activity and bioavailability of magnolol analogs – A potential for prostate cancer therapeutics Phytomedicine Plus Magnolol Prostate Cancer Antiandrogenic |
| title | Antiandrogenic activity and bioavailability of magnolol analogs – A potential for prostate cancer therapeutics |
| title_full | Antiandrogenic activity and bioavailability of magnolol analogs – A potential for prostate cancer therapeutics |
| title_fullStr | Antiandrogenic activity and bioavailability of magnolol analogs – A potential for prostate cancer therapeutics |
| title_full_unstemmed | Antiandrogenic activity and bioavailability of magnolol analogs – A potential for prostate cancer therapeutics |
| title_short | Antiandrogenic activity and bioavailability of magnolol analogs – A potential for prostate cancer therapeutics |
| title_sort | antiandrogenic activity and bioavailability of magnolol analogs a potential for prostate cancer therapeutics |
| topic | Magnolol Prostate Cancer Antiandrogenic |
| url | http://www.sciencedirect.com/science/article/pii/S2667031323000817 |
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