Research on the block of cell cycle and apoptosis induction on glioma cell line U251 of a novel HDAC inhibitor named DWP0016

Abstract

Abstract: Objective: Examine the effects of a novel HDAC inhibitor named DWP0016 on glioma cell line U251 and explore the molecular mechanisms underlying the cell cycle arrest and apoptosis induction. Methods: The anti-proliferative effects of DWP0016 were detected by MTT assays and the effects on the cell cycle arrest and apoptosis induction were examined by flow cytometry. The regulations on mRNA level of P21 and P53 were measured by Real-time PCR assay; the protein expressions of acetylation-H3，P21，P53，Pi3K，p-Pi3K，Akt and p-Akt were detected by Western blotting and measured by densitometry. Results: DWP0016 was found to inhibit the proliferation of U251 cell line at a much lower concentration（IC₅₀=0.531μmol· L^-1) than Oxaliplatin (IC₅₀=4.792μmol·L^-1). DWP0016 induced G₁ phase cell cycle arrest and apoptosis（P<0.05）while the acetylation of histone H3 was significantly up-regulated. The mRNA level and protein expression of tumor suppressor P21，P53 were up regulated whereas the protein expression of phosphorylation of Pi3K and Akt were down regulated. Conclusion: DWP0016 could effectively inhibit the proliferation of glioma cell line U251 and induce cell cycle arrest and apoptosis in U251 cells. The molecular mechanisms might relate to activate tumor suppressor P21，P53 and inhibit Pi3K/Akt cell signal pathway. All the results suggested that DWP0016 was a potent compound to be developed as an anti-glioma agent for clinic application in the future.

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Key words: Histone Deacetylases inhibitor（HDACi）, glioma, p21, p53, Pi3k/Akt pathway

JIN Hui, LIU Li-Feng, LIANG Lei, DENG Wei-Ping, LIU Jian-Wen. Research on the block of cell cycle and apoptosis induction on glioma cell line U251 of a novel HDAC inhibitor named DWP0016[J]. Acta Neuropharmacologica, 2011, 1(1): 38-45.

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