查尔酮衍生物L2H17对结肠癌发生的化学预防作用。
Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development.
作者信息
Xu Shanmei, Chen Minxiao, Chen Wenbo, Hui Junguo, Ji Jiansong, Hu Shuping, Zhou Jianmin, Wang Yi, Liang Guang
机构信息
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
Department of Radiology, the 5th Affiliated Hospital, Wenzhou Medical University, Lishui, Zhejiang, China.
出版信息
BMC Cancer. 2015 Nov 9;15:870. doi: 10.1186/s12885-015-1901-x.
BACKGROUND
Colon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer mortality worldwide. Chalcone and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. In addition, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. In our previous study, a group of chalcone derivatives were synthesized and exhibited strong anti-inflammatory activities. In this study, we evaluated the anti-cancer effects of the chalcone derivative, L2H17, in colon cancer cells.
METHODS
The cytotoxicities of L2H17 on various colon cancer cell lines were investigated by MTT and clonogenic assay. Cell cycle and apoptosis analysis were performed to evaluate the molecular mechanism of L2H17-mediated inhibition of tumor growth. Also, scratch wound and matrigel invasion experiments were performed to estimate the cell migration and invasion after L2H17 treatment. Finally, we observed the anti-colon cancer effects of L2H17 in vivo.
RESULTS
Our data show that compound L2H17 exhibited selective cytotoxic effect on colon cancer cells, via inducing G0/G1 cell cycle arrest and apoptosis in CT26.WT cells. Furthermore, L2H17 treatment decreased cell migration and invasion of CT26.WT cells. In addition, L2H17 possessed marked anti-tumor activity in vivo. The molecular mechanism of L2H17-mediated inhibition of tumor promotion and progression were function through inactivated NF-κB and Akt signaling pathways.
CONCLUSIONS
All these findings show that L2H17 might be a potential growth inhibitory chalcones derivative for colon cancer cells.
背景
结肠癌是全球第三大常见诊断癌症，也是癌症死亡的第二大主要原因。据报道，查尔酮及其衍生物在包括结肠癌细胞在内的多种癌细胞系中表现出抗癌作用。此外，查尔酮具有与DNA相互作用较弱和诱变风险较低等优点。在我们之前的研究中，合成了一组查尔酮衍生物并表现出强大的抗炎活性。在本研究中，我们评估了查尔酮衍生物L2H17对结肠癌细胞的抗癌作用。
方法
通过MTT和克隆形成试验研究L2H17对各种结肠癌细胞系的细胞毒性。进行细胞周期和凋亡分析以评估L2H17介导的肿瘤生长抑制的分子机制。此外，进行划痕伤口和基质胶侵袭实验以评估L2H17处理后细胞的迁移和侵袭能力。最后，我们观察了L2H17在体内的抗结肠癌作用。
结果
我们的数据表明，化合物L2H17对结肠癌细胞表现出选择性细胞毒性，通过诱导CT26.WT细胞的G0/G1细胞周期停滞和凋亡。此外，L2H17处理降低了CT26.WT细胞的迁移和侵袭能力。此外，L2H17在体内具有显著的抗肿瘤活性。L2H17介导的肿瘤促进和进展抑制的分子机制是通过使NF-κB和Akt信号通路失活来发挥作用的。
结论
所有这些发现表明，L2H17可能是一种潜在的对结肠癌细胞具有生长抑制作用的查尔酮衍生物。
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