Abstract
As the principal active ingredient in the Chinese herb Tripterygium wilfordii Hook.F (TwHF), triptolide has been shown to have very strong antitumor properties. The trimethylation of lysine 4 on histone H3 (H3K4me3) has been proposed to promote gene expression, and the accumulation of H3K4me3 at the transcriptional start sites of oncogenes is involved in carcinogenesis. To identify the association between the reduction of H3K4me3 and the apoptosis of MM cells induced by triptolide, we investigated the global patterns of H3K4me3 occupancy in the MM cell genome. Combined analyses using ChIP-on-chip and western blotting showed that H3K4me3 were highly enriched on the gene promoters of c-Myc and VEGFA and were associated with the up-regulation of both genes. Treatment of KM3 cells with triptolide and siRNA targeting ASH2L reduced the expression of c-Myc and VEGFA. These results suggest that triptolide can down-regulate c-Myc and VEGFA expression by blocking the accumulation of H3K4me3 on their promoters,and thus play an important role in anti-MM mechanism.
Keywords: Apoptosis, ASH2L, c-Myc, H3K4me3, Multiple myeloma, Triptolide, VEGFA.
Current Pharmaceutical Biotechnology
Title:Triptolide Induces Cell Apoptosis by Targeting H3K4me3 and Downstream Effector Proteins in KM3 Multiple Myeloma Cells
Volume: 17 Issue: 2
Author(s): Lu Wen, Yan Chen, Ling L. Zeng, Fei Zhao, Sha Yi, Li J. Yang, Ben P. Zhang, Jie Zhao, Zi C. Zhao and Chun Zhang
Affiliation:
Keywords: Apoptosis, ASH2L, c-Myc, H3K4me3, Multiple myeloma, Triptolide, VEGFA.
Abstract: As the principal active ingredient in the Chinese herb Tripterygium wilfordii Hook.F (TwHF), triptolide has been shown to have very strong antitumor properties. The trimethylation of lysine 4 on histone H3 (H3K4me3) has been proposed to promote gene expression, and the accumulation of H3K4me3 at the transcriptional start sites of oncogenes is involved in carcinogenesis. To identify the association between the reduction of H3K4me3 and the apoptosis of MM cells induced by triptolide, we investigated the global patterns of H3K4me3 occupancy in the MM cell genome. Combined analyses using ChIP-on-chip and western blotting showed that H3K4me3 were highly enriched on the gene promoters of c-Myc and VEGFA and were associated with the up-regulation of both genes. Treatment of KM3 cells with triptolide and siRNA targeting ASH2L reduced the expression of c-Myc and VEGFA. These results suggest that triptolide can down-regulate c-Myc and VEGFA expression by blocking the accumulation of H3K4me3 on their promoters,and thus play an important role in anti-MM mechanism.
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Cite this article as:
Wen Lu, Chen Yan, Zeng L. Ling, Zhao Fei, Yi Sha, Yang J. Li, Zhang P. Ben, Zhao Jie, Zhao C. Zi and Zhang Chun, Triptolide Induces Cell Apoptosis by Targeting H3K4me3 and Downstream Effector Proteins in KM3 Multiple Myeloma Cells, Current Pharmaceutical Biotechnology 2016; 17 (2) . https://dx.doi.org/10.2174/1389201016666150930115555
DOI https://dx.doi.org/10.2174/1389201016666150930115555 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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