Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells
Glioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of gli...
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MDPI AG
2021-09-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/9/1410 |
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| author | Hyeon Ji Kim Tae-Jun Kim Yu Gyung Kim Chaeeun Seong Jin-Hwa Cho Wanil Kim Kyung-Ha Lee Do-Yeon Kim |
| author_facet | Hyeon Ji Kim Tae-Jun Kim Yu Gyung Kim Chaeeun Seong Jin-Hwa Cho Wanil Kim Kyung-Ha Lee Do-Yeon Kim |
| author_sort | Hyeon Ji Kim |
| collection | DOAJ |
| description | Glioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of glioblastoma. Temozolomide, an FDA-approved alkylating agent, has been used as a first-line standard pharmacological approach, but several evident limitations were repeatedly reported. Despite additional therapeutic options suggested, there are no medications that successfully prevent a recurrence of glioblastoma and increase the five-year survival rate. In this study, we tested the possibility that finasteride has the potential to be developed as an anti-glioblastoma drug. Finasteride, an FDA-approved medication for the treatment of benign prostate hyperplasia and androgenic alopecia, is already known to pass through the blood–brain barrier and possess antiproliferative activity of prostate epithelial cells. We showed that finasteride inhibited the maintenance of glioma stem-like cells and repressed the proliferation of glioblastoma. Mechanistically, finasteride lowered intracellular ROS level by upregulating antioxidant genes, which contributed to inefficient β-catenin accumulation. Downregulated β-catenin resulted in the reduction in stemness and cell growth in glioblastoma. |
| first_indexed | 2024-03-10T07:18:43Z |
| format | Article |
| id | doaj.art-d36100ed8a524547993238114d2297ca |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T07:18:43Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d36100ed8a524547993238114d2297ca2023-11-22T14:47:18ZengMDPI AGPharmaceutics1999-49232021-09-01139141010.3390/pharmaceutics13091410Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma CellsHyeon Ji Kim0Tae-Jun Kim1Yu Gyung Kim2Chaeeun Seong3Jin-Hwa Cho4Wanil Kim5Kyung-Ha Lee6Do-Yeon Kim7Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, KoreaDepartment of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, KoreaDepartment of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, KoreaDepartment of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, KoreaDepartment of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, KoreaDepartment of Biochemistry, Department of Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDivision of Cosmetic Science and Technology, Daegu Haany University, Gyeongsan 38610, KoreaDepartment of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, KoreaGlioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of glioblastoma. Temozolomide, an FDA-approved alkylating agent, has been used as a first-line standard pharmacological approach, but several evident limitations were repeatedly reported. Despite additional therapeutic options suggested, there are no medications that successfully prevent a recurrence of glioblastoma and increase the five-year survival rate. In this study, we tested the possibility that finasteride has the potential to be developed as an anti-glioblastoma drug. Finasteride, an FDA-approved medication for the treatment of benign prostate hyperplasia and androgenic alopecia, is already known to pass through the blood–brain barrier and possess antiproliferative activity of prostate epithelial cells. We showed that finasteride inhibited the maintenance of glioma stem-like cells and repressed the proliferation of glioblastoma. Mechanistically, finasteride lowered intracellular ROS level by upregulating antioxidant genes, which contributed to inefficient β-catenin accumulation. Downregulated β-catenin resulted in the reduction in stemness and cell growth in glioblastoma.https://www.mdpi.com/1999-4923/13/9/1410glioblastomafinasterideproliferationβ-catenin |
| spellingShingle | Hyeon Ji Kim Tae-Jun Kim Yu Gyung Kim Chaeeun Seong Jin-Hwa Cho Wanil Kim Kyung-Ha Lee Do-Yeon Kim Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells Pharmaceutics glioblastoma finasteride proliferation β-catenin |
| title | Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells |
| title_full | Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells |
| title_fullStr | Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells |
| title_full_unstemmed | Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells |
| title_short | Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells |
| title_sort | antioxidant and antiproliferative activity of finasteride against glioblastoma cells |
| topic | glioblastoma finasteride proliferation β-catenin |
| url | https://www.mdpi.com/1999-4923/13/9/1410 |
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