Scholarlink

<p>Crotonoside (CTS) is a primary bioactive component found in Croton. current research has mainly focused on leukemia, with few reports in other cancers. Considering the traditional use of Croton, this study aims to evaluate the anti-colorectal cancer (CRC) activity of CTS and reveal its potential mechanisms. First, results in vitro show that CTS can markedly suppress CRC cell proliferation, invasion and migration, and EMT pathway (<i>P</i> &lt; 0.01). Then, RNA-seq analysis was employed to identify the core target and potential mechanism of CTS against CRC, and the results suggested KIF20A is a core target. Bioinformatic analysis showed that KIF20A is overexpressed in CRC and associated with a worse prognosis (<i>P</i> &lt; 0.01). KEGG and GO enrichment analyses indicated that anti-CRC activity of CTS is linked to the cell cycle. Next, Results confirmed that CTS can promote the expression of CDK1 and Cyclin B1 (<i>P</i> &lt; 0.01), and induces G2/M phase arrest to exert anti-CRC effects (<i>P</i> &lt; 0.01). Then, a subcutaneous tumor model was established in <i>vivo</i> to evaluate the anti-CRC activity of CTS; the results showed that CTS significantly inhibited CRC tumor growth and reduced both tumor weight and volume (<i>P</i> &lt; 0.01). CTS can suppress the expression of Ki67, E-cadherin, vimentin, and KIF20A (<i>P</i> &lt; 0.05), and promote the expression of Cyclin B1 and CDK1 (<i>P</i> &lt; 0.01). In addition, molecular docking analysis revealed that the binding energy of CTS to KIF20A was − 7.9&#xa0;kcal/mol, and CETSA assay showed that CTS treatment attenuated the thermal degradation of KIF20A protein. These results showed CTS can bind KIF20A tightly. Finally, overexpression of KIF20A reverses the anti-CRC effect of CTS. In summary, this study confirms that CTS can target and inhibit KIF20A, thereby inducing cell G2/M phase arrest and exerting anti-CRC effects.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Crotonoside exerts anti-colorectal cancer effects by suppressing KIF20A to regulate the cell cycle

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月20日

查看全文
  • Yu Zhang,
  • Jianguo Sun,
  • Zexu Chen

摘要

Crotonoside (CTS) is a primary bioactive component found in Croton. current research has mainly focused on leukemia, with few reports in other cancers. Considering the traditional use of Croton, this study aims to evaluate the anti-colorectal cancer (CRC) activity of CTS and reveal its potential mechanisms. First, results in vitro show that CTS can markedly suppress CRC cell proliferation, invasion and migration, and EMT pathway (P < 0.01). Then, RNA-seq analysis was employed to identify the core target and potential mechanism of CTS against CRC, and the results suggested KIF20A is a core target. Bioinformatic analysis showed that KIF20A is overexpressed in CRC and associated with a worse prognosis (P < 0.01). KEGG and GO enrichment analyses indicated that anti-CRC activity of CTS is linked to the cell cycle. Next, Results confirmed that CTS can promote the expression of CDK1 and Cyclin B1 (P < 0.01), and induces G2/M phase arrest to exert anti-CRC effects (P < 0.01). Then, a subcutaneous tumor model was established in vivo to evaluate the anti-CRC activity of CTS; the results showed that CTS significantly inhibited CRC tumor growth and reduced both tumor weight and volume (P < 0.01). CTS can suppress the expression of Ki67, E-cadherin, vimentin, and KIF20A (P < 0.05), and promote the expression of Cyclin B1 and CDK1 (P < 0.01). In addition, molecular docking analysis revealed that the binding energy of CTS to KIF20A was − 7.9 kcal/mol, and CETSA assay showed that CTS treatment attenuated the thermal degradation of KIF20A protein. These results showed CTS can bind KIF20A tightly. Finally, overexpression of KIF20A reverses the anti-CRC effect of CTS. In summary, this study confirms that CTS can target and inhibit KIF20A, thereby inducing cell G2/M phase arrest and exerting anti-CRC effects.