Antitumor activity of 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2,5-cyclohexadiene-1,4-dione isolated from the aerial part of Atractylodes macrocephala in hepatocellular carcinoma

碘化丙啶 细胞凋亡 膜联蛋白 体内 MTT法 激酶 下调和上调 流式细胞术 化学 MAPK/ERK通路 分子生物学 癌症研究 生物 细胞生物学 生物化学 程序性细胞死亡 生物技术 基因
作者
Lei Li,Rui Zhao,Ying Li,Wenhui Wang
出处
期刊:Molecular Medicine Reports [Spandidos Publishing]
卷期号:16 (5): 6299-6305 被引量:8
标识
DOI:10.3892/mmr.2017.7385
摘要

2‑[(2E)‑3,7‑dimethyl‑2,6‑octadienyl]‑6‑methy l‑2,5‑cyclohexadiene‑1,4‑dione (DMD) is a compound isolated from Atractylodes macrocephala; however, its antitumor activity has not yet been investigated. Therefore, the present study aimed to investigate the antitumor activity of DMD in the H22 mouse hepatocellular carcinoma (HCC) cell line in vitro and in vivo. In the present study, the antiproliferative effects of DMD against H22 cells were evaluated using the MTT assay in vitro. Furthermore, xenograft nude mice were established to evaluate the antitumor effects of DMD on H22 cells in vivo. In addition, apoptosis of H22 cells was determined by flow cytometry with Annexin V‑fluorescein isothiocyanate/propidium iodide staining, and western blotting was subsequently performed to examine the expression levels of proteins associated with apoptosis, and c‑Jun N‑terminal kinase (JNK), p38 and extracellular signal‑regulated kinase (ERK)1/2 mitogen‑activated protein kinases (MAPKs). The results demonstrated that DMD exerts an antitumor effect against H22 cells in vitro and in vivo, and the underlying mechanism may be associated with mitochondria‑mediated apoptosis through upregulation of cytochrome c, cleaved (c)‑caspase‑3, c‑caspase‑9, c‑caspase‑7 and B‑cell lymphoma 2 (Bcl‑2)‑associated X protein, and downregulation of Bcl‑2. In addition, the antitumor effects of DMD against H22 cells may be also associated with the MAPK signaling pathway via increased p‑JNK and reduced p‑ERK1/2 expression. In conclusion, the present study demonstrated the DMD exerts antitumor effects against HCC in mice and provides a scientific basis for the clinical use of DMD for the treatment of HCC.
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