Laboratory of Immunopathology of Neglected Diseases and Cancer, State University of Londrina - UEL. Rodovia Celso Garcia Cid Campus Zip Code 86057-970, Post Box 10.011. Londrina, PR, Brazil.
Laboratory of Immunopathology of Neglected Diseases and Cancer, State University of Londrina - UEL. Rodovia Celso Garcia Cid Campus Zip Code 86057-970, Post Box 10.011. Londrina, PR, Brazil.
Phytomedicine. 2021 Jan;80:153373. doi: 10.1016/j.phymed.2020.153373. Epub 2020 Oct 9.
Hepatocellular Carcinoma (HCC) is extremely aggressive and presents low rates of response to the available chemotherapeutic agents. Many studies have focused on the search for alternative low-cost natural compounds with antiproliferative potential that selectively respond to liver cancer cells.
This study assessed the in vitro direct action of trans-chalcone (TC) on cells of the human HCC HuH7.5 cell line.
We subjected the HuH7.5 tumor cells to TC treatment at increasing concentrations (12.5-100 µM) for 24 and 48 h. Cell viability was verified through MTT and 50% inhibitory concentration of cells (IC 23.66 µM) was determined within 48 h. We quantified trypan blue proliferation and light microscopy, ROS production, mitochondrial depolarization and autophagy, cell cycle analysis, and apoptosis using Muse® cell analyzer and immunocytochemical markings of p53 and β-catenin.
Data showed an effective dose- and time-dependent TC-cytotoxic action at low micromolar concentrations without causing toxicity to non-cancerous cells, such as erythrocytes. TC-treatment caused mitochondrial membrane damage and cell cycle G0/G1 phase arrest, increasing the presence of the p53 protein and decreasing β-catenin, in addition, to inducing cell death by autophagy. Additionally, TC decreased the metastatic capacity of HuH7.5, which affected the migration/invasion of this type of cell.
In vitro TC activity in the human HCC HuH7.5 tumor cell line is shown to be a potential molecule to develop new therapies to repair the p53 pathway and prevent the overexpression of Wnt/β-catenin tumor development inducing autophagy cell death and decreasing metastatic capacity of HuH7.5 cell line.
肝细胞癌 (HCC) 极具侵袭性，对现有化疗药物的反应率较低。许多研究都集中在寻找具有抗增殖潜力的替代低成本天然化合物上，这些化合物可以选择性地作用于肝癌细胞。
本研究评估了反式查尔酮 (TC) 对人 HCC HuH7.5 细胞系细胞的体外直接作用。
我们用不同浓度的 TC（12.5-100µM）处理 HuH7.5 肿瘤细胞 24 和 48 小时。通过 MTT 验证细胞活力，并在 48 小时内确定细胞的 50%抑制浓度 (IC 23.66µM)。我们使用 Muse®细胞分析仪定量台盼蓝增殖和相差显微镜观察、ROS 产生、线粒体去极化和自噬、细胞周期分析以及 p53 和 β-连环蛋白的免疫细胞化学标记来评估细胞增殖。
数据显示，TC 在低微摩尔浓度下具有有效剂量和时间依赖性的细胞毒性作用，而不会对非癌细胞（如红细胞）造成毒性。TC 处理导致线粒体膜损伤和细胞周期 G0/G1 期阻滞，增加 p53 蛋白的表达，降低 β-连环蛋白的表达，此外还通过自噬诱导细胞死亡。此外，TC 降低了 HuH7.5 的转移能力，影响了这种类型细胞的迁移/侵袭。
在人 HCC HuH7.5 肿瘤细胞系中，TC 的体外活性显示出作为一种潜在分子的潜力，可以开发新的治疗方法来修复 p53 途径，防止 Wnt/β-连环蛋白肿瘤过度表达诱导自噬细胞死亡，并降低 HuH7.5 细胞系的转移能力。
