From epidemiology and neurodevelopment to antineoplasticity. Medroxyprogesterone reduces human glial tumor growth in vitro and C6 glioma in rat brain in vivo.

Abstract

OBJECTIVE:

Glial tumor growth may accelerate during gestation, but epidemiological studies consistently demonstrated that parousity reduces life long risk of glial tumors. Pregnancy may also accelerate growth of medulloblastoma and meningioma, but parousity does not confer protection against these tumors. We were the first to show that medroxyprogesterone acetate (MPA) reduces rat C6 glioma growth in vitro. Now we aimed to determine the effects of MPA on human brain cancers (particularly glioblastoma) in vitro and C6 glioma in vivo.

PATIENTS AND METHODS:

We evaluated the effects of MPA on: i) monolayer growth of human U87 and U251 glioblastoma, ii) 3D-spheroid growth and invasion of C6 rat glioma and human U251 glioma, iii) interactions with PI3-Kinase inhibitors and coxsackie-adenovirus receptor (CAR) in modifying 3D-spheroid invasion of glioma.

RESULTS:

MPA at low doses (3.25-13 μM) insignificantly stimulated and at high doses (above 52 μM) strongly suppressed the growth of human U87 and U251 cells in vitro. MPA also binds to glucocorticoid receptors similar to dexamethasone (Dex) and unexpectedly, PI3-Kinase inhibitors at low doses suppressed anti-invasive efficacies of MPA and Dex. MPA exerted higher invasion-inhibitory effects on CAR-expressing human glioma cells. Lastly, MPA suppressed growth of C6 glioma implanted into rat brain.

CONCLUSION:

Progesterone analogues deserve to be studied in future experimental models of high grade glial brain tumors.

• Authors: Meric A Altinoz, Josephine Nalbantoglu, Aysel Ozpinar, M Emin Ozcan, Rolando F Del Maestro, Ilhan Elmaci
• Journal: Clinical neurology and neurosurgery (Clin Neurol Neurosurg) Vol. 173 Pg. 20-30 (10 2018) ISSN: 1872-6968 [Electronic] Netherlands
• PMID: 30055402 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Dexamethasone
• Medroxyprogesterone

Topics

• Animals
• Brain (drug effects, pathology)
• Brain Neoplasms (drug therapy, pathology)
• Cerebellar Neoplasms (drug therapy)
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Glioblastoma (drug therapy, pathology)
• Glioma (drug therapy, pathology)
• Humans
• Medroxyprogesterone (pharmacology)
• Meningioma (drug therapy)
• Rats
• Tumor Cells, Cultured (drug effects)