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Oncology reports

Roscovitine has anti-proliferative and pro-apoptotic effects on glioblastoma cell lines: A pilot study.


PMID 26151768

Abstract

Purine analogue roscovitine, a cyclin-dependent kinase (CDK) inhibitor, has shown strong anti-proliferative and pro-apoptotic effects in solid and hematologic cancers such as non small-cell lung cancer and lymphomas. It targets CDK2, 7 and 9 preferentially, which are also overexpressed in glioblastoma. Τherefore, the biological effects of roscovitine in glioblastoma cell lines were investigated. Glioblastoma A172 and G28 cell lines were incubated with serial concentrations of roscovitine for 24-120xa0h. Proliferation was measured using the xCELLigence Real-Time Cell Analyzer, an impedance‑based cell viability system. Cell cycle distribution was assessed by flow cytometry and gene expression was quantified by quantitative RT-PCR and western blot analysis. Roscovitine exhibited a clear dose-dependent anti‑proliferative and pro‑apoptotic effect in the A172xa0cell line, while G28xa0cells showed a anti-proliferative effect only at 100xa0µM. The results of the flow cytometric (FACS) analysis revealed a dose-dependent increase of the G2/M and sub-G1xa0fractions in A172xa0cells, while G28xa0cells responded with an elevated sub-G1xa0fraction only at the highest concentration. Roscovitine led to a dose‑dependent decrease of transcripts of p53, CDKxa07 and cyclinsxa0A and E and an increase of >4-fold of p21 in A172xa0cells. In G28xa0cells, a dose‑dependent induction of CDK2, p21 and cyclinxa0D was observed between 10 and 50xa0µM roscovitine after 72xa0h, however, at the highest concentration of 100xa0µM, all investigated genes were downregulated. Roscovitine exerted clear dose-dependent anti-proliferative and pro-apoptotic effects in A172xa0cells and less distinct effects on G28xa0cells. In A172xa0cells, roscovitine led to G2/Mxa0arrest and induced apoptosis, an effect accompanied by induced p21 and a reduced expression of CDK2, 7 and 9 and cyclinsxa0A andxa0E. These effects requre further studies on a larger scale to confirm whether roscovitine can be used as a therapeutic agent against glioblastoma.