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      Dutasteride combined with androgen receptor antagonists inhibit glioblastoma U87 cell metabolism, proliferation, and invasion capacity: Androgen regulation.

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          Abstract

          Glioblastoma (GB) is the most common and aggressive primary brain tumor in adult humans. Therapeutic resistance and tumor recurrence after surgical resection contributes to a poor prognosis for glioblastoma patients. Men are known to be more likely than women to develop an aggressive form of GB. Although the reasons for this disparity remain poorly understood, differences in sex steroids have emerged as a leading explanation. Studies indicate that GB-derived cells express androgen receptors (ARs) and synthesize androgens, suggesting that androgens may have a role in the tumor pathogenesis. Thus, our objective was to investigate the effects of the 5α-reductase enzyme inhibitor dutasteride, the AR antagonists cyproterone and flutamide, and combinations of these drugs on the metabolism, proliferation, and invasion capacity of GB-derived U87 cells. We also examined the effects of three natural androgens testosterone, androstenedione and dihydrotestosterone (T, A4, and DHT) on these cells. Cell metabolism was investigated by MTT assay, proliferation was assessed by the bromodeoxyuridine (BrdU) incorporation assay, and invasion was assessed by Boyden chamber assay. The results revealed that T and especially DHT, but not A4, increased U87 cell metabolism and proliferation. Following these findings, we examined the effect of adding dutasteride, cyproterone, or flutamide to the culture media and found that they all significantly decreased cell metabolism and proliferation. Dutasteride also significantly reduced cell invasion. Moreover, any combination of these drugs enhanced their inhibitory effects; the combination of dutasteride to flutamide was most effective at decreasing GB cell proliferation. Our results suggest that administering a combination of AR antagonists and enzyme blockers may be a more effective alternative treatment for GB.

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          Author and article information

          Journal
          Steroids
          Steroids
          Elsevier BV
          1878-5867
          0039-128X
          December 2020
          : 164
          Affiliations
          [1 ] Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV del IPN, Ciudad de México, México.
          [2 ] Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Ciudad de Mexico, Mexico.
          [3 ] Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Ciudad de México, México.
          [4 ] Departamento de Fisiología, Biofísica y Neurociencias, CINVESTAV del IPN, Ciudad de México, México. Electronic address: mromano@fisio.cinvestav.mx.
          Article
          S0039-128X(20)30159-8
          10.1016/j.steroids.2020.108733
          32980365
          385d35d3-d8ef-4263-aef5-cfa1b3e162bd
          Copyright © 2020 Elsevier Inc. All rights reserved.
          History

          Androgens,Cancer,Cyproterone,Dutasteride,Finasteride,Glioblastoma

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