Abstract
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.
Highlights
Glioblastoma is highly aggressive and devastating primary brain tumor
We showed that cancer stem-like cell populations were enriched by maintaining cells with serum-free culture media supplemented with epidermal growth factor (EGF) and basic fibroblast growth factor [14]
Similar to temozolomide, finasteride reduced the sphere size of glioblastoma or even made cells grow in monolayer, suggesting that finasteride suppresses the stemness of cancer stem-like cells in glioblastoma (Figure 1A)
Summary
Glioblastoma is highly aggressive and devastating primary brain tumor. it has been regarded as a rare cancer with comparatively low incidence (approximately5 per 100,000 persons) [1], glioblastoma is infamous for short median survival time (12 to18 months) and desperate five-year survival rate (6.8%) [2]. Glioblastoma is highly aggressive and devastating primary brain tumor It has been regarded as a rare cancer with comparatively low incidence Due to extremely infiltrative nature of glioblastoma, residual infiltrating tumor cells commonly exist surrounding the visible tumor mass, which are not identified by radiographic imaging [4]. For this reason, pharmacotherapy is strongly required after surgical management for glioblastoma patients. Radiation plus concomitant and adjuvant temozolomide provided 2.5 months of the median survival benefit and significantly improved the two-year survival rate from 10.4% to 26.5% [5], leading to the use of temozolomide as a first-line standard approach against glioblastoma.
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