In Vitro and In Vivo Antitumor Activity of Vitamin D3 in Malignant Gliomas: A Systematic Review.

Context: The most common type of brain tumors are gliomas, among which glioblastoma multiforme is the most life-threatening. In spite of the existing treatments, malignant gliomas often do not respond to treatment. Objectives: The aim of this study was to investigate the antitumor activity of vitamin D3 in malignant gliomas through the study of in vitro and in vivo articles. Data Sources: The electronic databases, including PubMed, ScienceDirect, Webof Science, Google Scholar, and the Cochrane Central Register of Clinical Trials (last updated April 12th, 2019) were searched, using medical subject headings (MeSH) keywords "vitamin D AND brain malignancy". Data Extraction: There was no limitation on the date and language of the articles. A review of all the found articles at the level of titles and abstracts was made to find eligible articles. Our work is in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The quality of the articles was judged in accordance with the GRADE tool for in vitro studies and CIRCLEs RoB tool for in vivo studies. Results: Totally, 88 articles were identified and after careful examination, 16 eligible articles meeting the inclusion criteria were selected. These studies showed that vitamin D3 and its analogs suppress self-renewal ability, cell viability and/or cell growth, migration rate, and invasive capacity; in addition, they induce autophagy and cell death. They also reduce tumor size in animal models. Evidence was mainly of moderate to high quality. Conclusions: Based on the in vitro and in vivo evidence of this systematic review, vitamin D3, compared to the control group, induced cell death and reduced cell growth, invasion, and migratory capacity in gliomas cell culture. As well as, vitamin D analogs were able to show the same effects without the hypercalcemic effect in vivo. We suggest performing future high-quality studies with the aim of shedding light on the relevant mechanisms and the effects of vitamin D3 derivatives and its analogs on health status and clinical outcomes in patients with malignant gliomas. [ABSTRACT FROM AUTHOR]