Lappaol F（LAF）是一种从牛蒡（菊科）中提取的天然木脂素，在体内和体外能够抑制肿瘤细胞的生长。其背后的机制涉及抑制“是的”相关蛋白。然而，LAF在细胞周期调节中的特定作用尚未知晓。本研究确定了LAF调节细胞周期进程的分子机制。将不同的结肠癌细胞系（SW480、HCT15和HCT116）经过LAF（25、50和75μmol/L）处理48小时。通过苏菲红B和流式细胞仪检测LAF对细胞增殖和细胞周期的影响。使用定量蛋白质组学识别差异表达蛋白（DEPs）。通过基因本体论和Kyoto基因与基因组百科全书分析DEPs的生物信息学进行分析。使用RT-qPCR和western blotting分析细胞周期通路内的DEPs的表达水平。LAF抑制了SW480、HCT15和HCT116细胞的增殖（IC50分别为47.1、51.4和32.8μmol/L），并引起了细胞周期在S期的停滞。共识别和定量了6331个蛋白质，其中127个蛋白质在LAF处理组和未处理组之间差异表达。GO和KEGG富集分析表明DEPs主要参与细胞周期。CDKN1C/p57的差异表达最显着，其表达倍数最高（3.155倍）。CDKN1C/p57的敲除影响了LAF引起的S期细胞周期停滞和增殖抑制。LAF通过激活CDKN1C/p57在结肠癌细胞中诱导S期停滞的抗肿瘤效应。

Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumor cell growth in vitro and in vivo. The underlying mechanism involves the suppression of the Yes-associated protein. However, the specific role of LAF in cell cycle regulation remains unknown.This study determined the molecular mechanism by which LAF regulates cell cycle progression.Various colon cancer cell lines (SW480, HCT15, and HCT116) were treated with LAF (25, 50, and 75 μmol/L) for 48 h. The effects of LAF on cell proliferation and cell cycle were determined using sulforhodamine B and flow cytometry assays. Differentially expressed proteins (DEPs) were identified using quantitative proteomics. Bioinformatic analysis of DEPs was conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Expression levels of DEPs in the cell cycle pathway were analyzed using RT-qPCR and western blotting.LAF suppressed the proliferation of SW480, HCT15, and HCT116 cells (IC50 47.1, 51.4, and 32.8 μmol/L, respectively) and induced cell cycle arrest at the S phase. A total of 6331 proteins were identified and quantified, of which 127 were differentially expressed between the LAF-treated and untreated groups. GO and KEGG enrichment analyses revealed that DEPs mainly participated in the cell cycle. CDKN1C/p57 showed the most significant differential expression, with the highest fold-change (3.155-fold). Knockdown of CDKN1C/p57 attenuated the S phase cell cycle arrest and proliferation inhibition induced by LAF.LAF exerts antitumor effects via S phase arrest by activating CDKN1C/p57 in colorectal cancer cells.