核糖体蛋白s6
细胞凋亡
PI3K/AKT/mTOR通路
磷酸化
EIF4E公司
癌细胞
激酶
细胞生物学
缺氧(环境)
生物
缺氧诱导因子
P70-S6激酶1
蛋白质生物合成
蛋白激酶A
癌症研究
化学
信使核糖核酸
分子生物学
癌症
生物化学
翻译(生物学)
基因
遗传学
有机化学
氧气
作者
Chunliu Mi,Qiuli Zhang,Mengjun Sun,You Li,Sun Qilin,Shao‐Lei Geng,Tianyun Wang
标识
DOI:10.1016/j.intimp.2024.112066
摘要
Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers.
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