National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing Collaborative Innovation Center of Targeted and Innovative Therapeutics, College of Pharmacy & International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, China.
Integrative Cancer Center & Cancer Clinical Research Center, Sichuan Cancer Hospital & Institute Sichuan Cancer Center, School of Medicine University of Electronic Science and Technology of China, Chengdu 610041, China.
Biomed Res Int. 2020 Aug 25;2020:4929053. doi: 10.1155/2020/4929053. eCollection 2020.
Cancer remains a major clinical challenge because of the lack of effective drug for its treatment. To find out novel cancer chemotherapeutic molecules, we explored the anticancer effect of novel imidazopyridine compound and also investigated the underlying molecular mechanism.
Human cervical cancer cell (HeLa) viability was measured by an MTT assay after treatment with compound . Clonogenicity of HeLa cells was investigated by an in vitro colony formation assay. Cell death was visualized by propidium iodide (PI) staining. Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and mitochondrial membrane potential in HeLa cells. The expression level of apoptosis-related proteins was also determined by western blot.
Compound suppressed HeLa cell viability in a time- and dose-dependent manner. Compound induced mitochondrial outer membrane permeabilization (MOMP), activated caspase cascade, and finally resulted in apoptosis.
Compound induces mitochondrial pathway-mediated apoptosis in human cervical cancer cells, suggesting that could be a potential lead compound to be developed as a cancer therapeutic molecule.
由于缺乏有效的癌症治疗药物，癌症仍然是一个主要的临床挑战。为了寻找新的癌症化学治疗分子，我们探索了新型咪唑并吡啶化合物的抗癌作用，并研究了其潜在的分子机制。
用 MTT 法检测化合物处理后人宫颈癌（HeLa）细胞活力。用体外集落形成实验研究 HeLa 细胞的集落形成能力。碘化丙啶（PI）染色观察细胞死亡。用流式细胞术（FACS）检测 HeLa 细胞凋亡和线粒体膜电位。用 Western blot 测定凋亡相关蛋白的表达水平。
化合物 呈时间和剂量依赖性抑制 HeLa 细胞活力。化合物 诱导线粒体外膜通透性（MOMP），激活 caspase 级联，最终导致细胞凋亡。
化合物 诱导人宫颈癌细胞中线粒体途径介导的细胞凋亡，提示 可能是一种有潜力的先导化合物，可开发为癌症治疗分子。
