Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, PR China.
Mol Med Rep. 2012 Jul;6(1):185-90. doi: 10.3892/mmr.2012.891. Epub 2012 Apr 26.
β-Elemene is extracted from the Chinese medicinal herb Curcuma Wenyujin. It has a broad-spectrum antitumor effect on many types of cancer. However, the exact mechanism of action of β-elemene in hepatocellular carcinoma (HCC) remains unknown. Histone H1 is thought to act as a repressor of transcription by promoting the compaction of chromatin into higher order structures. We found that histone H1 plays an important role in the antitumor function of β-elemene. In this study, histone H1 expression in the H22 murine hepatocellular carcinoma cell line was confirmed, with P388D1 cells serving as a positive control. Furthermore, H22 cells were cultured with β-elemene for different time-points in vitro and treated with different dose-dependent β-elemene in an experimental H22 HCC xenograft transplantation model to confirm whether β-elemene inhibited the growth of H22 tumor cells. In addition, measurements of histone H1 expression both in vitro and in vivo enabled us to demonstrate that β-elemene affects the expression of histone H1 only at the protein level, but is not involved in regulation at the gene level. Our results clearly show that the effect of β-elemene on inhibiting the growth of H22 tumor cells is time- and dose-dependent. In conclusion, β-elemene inhibits the growth of H22 cells by enhancing the expression of histone H1 only at the protein level. This finding may provide insight into a new mechanism of the antitumor action of β-elemene.
β-榄香烯从中国草药莪术中提取，对多种癌症具有广谱的抗肿瘤作用。然而，β-榄香烯在肝癌（HCC）中的确切作用机制尚不清楚。组蛋白 H1 被认为通过促进染色质凝聚成更高阶结构来充当转录的抑制剂。我们发现组蛋白 H1 在β-榄香烯的抗肿瘤功能中起重要作用。在这项研究中，确认了 H22 鼠肝癌细胞系中组蛋白 H1 的表达，以 P388D1 细胞作为阳性对照。此外，体外培养 H22 细胞不同时间点，并在实验性 H22 HCC 异种移植移植模型中用不同剂量依赖性β-榄香烯处理，以确认β-榄香烯是否抑制 H22 肿瘤细胞的生长。此外，在体外和体内测量组蛋白 H1 的表达使我们能够证明β-榄香烯仅在蛋白质水平上影响组蛋白 H1 的表达，而不涉及基因水平的调节。我们的结果清楚地表明，β-榄香烯抑制 H22 肿瘤细胞生长的作用呈时间和剂量依赖性。总之，β-榄香烯通过仅在蛋白质水平上增强组蛋白 H1 的表达来抑制 H22 细胞的生长。这一发现可能为β-榄香烯的抗肿瘤作用提供新的机制见解。
