细胞凋亡
MAPK/ERK通路
细胞周期
癌症研究
细胞周期蛋白依赖激酶1
细胞生长
细胞周期检查点
生物
小桶
信号转导
化学
癌变
髓系白血病
癌症
细胞生物学
转录组
生物化学
基因表达
遗传学
基因
作者
Lijie Gong,Chen Chen,Xiaoqin Liu,Xianjian Wu,Ling Zhu,Jian-Guang Luo,Ling-Yi Kong
标识
DOI:10.1016/j.taap.2022.116249
摘要
Hainanolide (HN) is a norditerpenoid metabolite extract from Cephalotaxus fortunei Hook. f. C. fortunei Hook. f. is renowned for the active alkaloids, such as harringtonine (HT) and homoharringtonin (HTT), which have been clinically used to treat chronic myeloid leukemia. Nowadays, diterpenoids, another important metabolite, attracted the attention of chemists. Among them, Hainanolide (HN), a cephalotane-type diterpenoid, has been proven to possess potent antitumor activities. However, the underlying therapeutic mechanisms of HN in anti-tumor have not been investigated yet. Our present study demonstrated that HN inhibited HCT-116 and HCT-15 cell proliferation in a dose- and time-dependent manner. Further studies demonstrated that HN can induce G2/M phase arrest and alter the Cdc25C/Cdc2/CyclinB1 proteins. Western blot indicated that HN promoted apoptosis by up-regulating Bax and down-regulated Bcl-2. And the caspase-3 and caspase-9 activities of HCT-116 and HCT-15 cells were increased. Transcriptome analysis is used to reveal the possible mechanism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested the genes were mainly enriched in the MAPK signaling pathway. Certainly, HN activates MAPK signaling pathway. In vivo, HN prevented the AOM/DSS-induced tumorigenesis of colon cancer in C57BL/6 mice. Our study indicated that HN inhibits the progression of colon cancer cells by blocking the cell cycle, inducing apoptosis, and activating the MAPK pathway. This study provides a theoretical and experimental scientific basis for future investigations of the antitumor effects of HN against colon cancer.
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