Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro
Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/12338 |
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| author | Aleksandar Kuzmanov Souzan Salemi Florian A. Schmid Irene A. Burger Daniel Eberli Benedikt Kranzbühler |
| author_facet | Aleksandar Kuzmanov Souzan Salemi Florian A. Schmid Irene A. Burger Daniel Eberli Benedikt Kranzbühler |
| author_sort | Aleksandar Kuzmanov |
| collection | DOAJ |
| description | Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful to further improve the detection rate of PSMA-based imaging. To achieve this, we tested dutasteride (Duta)—generally used for treatment of benign prostatic enlargement—and lovastatin (Lova)—a compound used to reduce blood lipid concentrations. We aimed to compare the individual effects of Duta and Lova on cell proliferation as well as PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. Our results show that a treatment with ≤1 μM Duta and ≥1 μM Lova lead to a significant upregulation of whole and cell surface PSMA expression in LNCaP, C4-2 and VCaP cells. Lower concentrations of Duta and Lova in combination (0.5 μM Duta + 0.5 μM Lova or 0.5 μM Duta + 1 μM Lova) were further capable of enhancing PSMA protein expression compared to a single compound treatment using higher concentrations in all tested cell lines (LNCaP, C4-2 and VCaP). |
| first_indexed | 2024-03-11T00:25:46Z |
| format | Article |
| id | doaj.art-c94ef57b01604af286ac251247b06add |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:25:46Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c94ef57b01604af286ac251247b06add2023-11-18T23:03:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124151233810.3390/ijms241512338Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In VitroAleksandar Kuzmanov0Souzan Salemi1Florian A. Schmid2Irene A. Burger3Daniel Eberli4Benedikt Kranzbühler5Laboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zürich, University of Zurich, 8091 Zurich, SwitzerlandLaboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zürich, University of Zurich, 8091 Zurich, SwitzerlandLaboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zürich, University of Zurich, 8091 Zurich, SwitzerlandDepartment of Nuclear Medicine, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandLaboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zürich, University of Zurich, 8091 Zurich, SwitzerlandLaboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zürich, University of Zurich, 8091 Zurich, SwitzerlandProstate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful to further improve the detection rate of PSMA-based imaging. To achieve this, we tested dutasteride (Duta)—generally used for treatment of benign prostatic enlargement—and lovastatin (Lova)—a compound used to reduce blood lipid concentrations. We aimed to compare the individual effects of Duta and Lova on cell proliferation as well as PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. Our results show that a treatment with ≤1 μM Duta and ≥1 μM Lova lead to a significant upregulation of whole and cell surface PSMA expression in LNCaP, C4-2 and VCaP cells. Lower concentrations of Duta and Lova in combination (0.5 μM Duta + 0.5 μM Lova or 0.5 μM Duta + 1 μM Lova) were further capable of enhancing PSMA protein expression compared to a single compound treatment using higher concentrations in all tested cell lines (LNCaP, C4-2 and VCaP).https://www.mdpi.com/1422-0067/24/15/12338prostate-specific membrane antigen (PSMA)androgen receptor (AR)dutasteride (Duta)lovastatin (Lova)dutasteride + lovastatin (Duta + Lova) treatment |
| spellingShingle | Aleksandar Kuzmanov Souzan Salemi Florian A. Schmid Irene A. Burger Daniel Eberli Benedikt Kranzbühler Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro International Journal of Molecular Sciences prostate-specific membrane antigen (PSMA) androgen receptor (AR) dutasteride (Duta) lovastatin (Lova) dutasteride + lovastatin (Duta + Lova) treatment |
| title | Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro |
| title_full | Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro |
| title_fullStr | Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro |
| title_full_unstemmed | Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro |
| title_short | Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro |
| title_sort | improved prostate specific membrane antigen psma stimulation using a super additive effect of dutasteride and lovastatin in vitro |
| topic | prostate-specific membrane antigen (PSMA) androgen receptor (AR) dutasteride (Duta) lovastatin (Lova) dutasteride + lovastatin (Duta + Lova) treatment |
| url | https://www.mdpi.com/1422-0067/24/15/12338 |
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