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.

Hainanolide (HN) 是一种来自三尖杉的降二萜代谢物提取物。F。C.fortunei钩。F。以活性生物碱而闻名，例如三尖杉酯碱 (HT) 和高三尖杉酯 (HTT)，已在临床上用于治疗慢性粒细胞白血病。如今，另一种重要的代谢产物二萜类化合物引起了化学家的关注。其中，海南内酯 (HN) 是一种头孢菌素类二萜类化合物，已被证明具有强大的抗肿瘤活性。然而，HN 在抗肿瘤方面的潜在治疗机制尚未得到研究。我们目前的研究表明，HN 以剂量和时间依赖性方式抑制 HCT-116 和 HCT-15 细胞增殖。进一步的研究表明，HN 可以诱导 G2/M 期阻滞并改变 Cdc25C/Cdc2/CyclinB1 蛋白。Western blot表明HN通过上调Bax和下调Bcl-2促进细胞凋亡。并且HCT-116和HCT-15细胞的caspase-3和caspase-9活性升高。转录组分析用于揭示可能的机制。京都基因与基因组百科全书 (KEGG) 分析表明，这些基因主要富集在 MAPK 信号通路中。当然，HN 激活了 MAPK 信号通路。在体内，HN 阻止了 C57BL/6 小鼠中 AOM/DSS 诱导的结肠癌肿瘤发生。我们的研究表明，HN 通过阻断细胞周期、诱导细胞凋亡和激活 MAPK 通路来抑制结肠癌细胞的进展。本研究为今后研究HN对结肠癌的抗肿瘤作用提供了理论和实验科学依据。京都基因与基因组百科全书 (KEGG) 分析表明，这些基因主要富集在 MAPK 信号通路中。当然，HN 激活了 MAPK 信号通路。在体内，HN 阻止了 C57BL/6 小鼠中 AOM/DSS 诱导的结肠癌肿瘤发生。我们的研究表明，HN 通过阻断细胞周期、诱导细胞凋亡和激活 MAPK 通路来抑制结肠癌细胞的进展。本研究为今后研究HN对结肠癌的抗肿瘤作用提供了理论和实验科学依据。京都基因与基因组百科全书 (KEGG) 分析表明，这些基因主要富集在 MAPK 信号通路中。当然，HN 激活了 MAPK 信号通路。在体内，HN 阻止了 C57BL/6 小鼠中 AOM/DSS 诱导的结肠癌肿瘤发生。我们的研究表明，HN 通过阻断细胞周期、诱导细胞凋亡和激活 MAPK 通路来抑制结肠癌细胞的进展。本研究为今后研究HN对结肠癌的抗肿瘤作用提供了理论和实验科学依据。我们的研究表明，HN 通过阻断细胞周期、诱导细胞凋亡和激活 MAPK 通路来抑制结肠癌细胞的进展。本研究为今后研究HN对结肠癌的抗肿瘤作用提供了理论和实验科学依据。我们的研究表明，HN 通过阻断细胞周期、诱导细胞凋亡和激活 MAPK 通路来抑制结肠癌细胞的进展。本研究为今后研究HN对结肠癌的抗肿瘤作用提供了理论和实验科学依据。