Pseudolaric acid B inhibits neuroglioma cell proliferation through DNA damage response.

Abstract

Human neuroglioma is one of the most common malignant intracranial tumors in neurosurgery, and accounts for more than 50% of all brain cancer cases. Thus, a clinically effective drug with which to treat neuroglioma is urgently required. Pseudolaric acidB (PAB), a diterpene acid isolated from the root and trunk bark of Pseudolarixkaempferi Gordon (Pinaceae), was found to inhibit cell growth in a variety of cancer cell lines, but to date the effect of PAB on neuroglioma remains unclear. MTT analysis confirmed that PAB inhibited neuroglioma A172 cell growth in a time-anddose-dependent manner. In addition, PAB influenced the aggregation of tubulin in A172 cells. Meanwhile following PAB treatment, a higher percentage of cells accumulated in the G2/Mphase from 12to48h, while at 36h, cell cycle slippage into the G0/G1 phase, and at 48h, slippage into the Sphase was observed using flow cytometric analysis. Corresponding protein expression was consistent with the cell cycle alteration as detected by western blotting, and it was speculated that cell cycle slippage was related to reduced effectiveness of PAB which warrants further investigation. Meanwhile PAB induced cell death by regulating p38, ERK and JNK expression and activating the DNA damage response. Therefore, PAB plays an antitumor role in A172 cells, and may be a candidate drug for neuroglioma therapy.