PDF(Pubmed)
Abstract：
Although fangchinoline has been widely used as an adjunct therapy for a variety of inflammatory and cancerous diseases, its mechanism of action on tumor cells remains unclear. Fangchinoline derivative LYY-35 reduced the number of A549 cells, deformed cell morphology and increased cell debris. Cell viability was significantly reduced, while the same concentration of LYY-35 had little effect on BEAS-2B viability of normal lung epithelial cells. In addition, LYY-35 can also reduce the migration, proliferation and invasion ability of A549 cells. Levels of β-catenin, ZO-1 and ZEB-1 proteins, biomarkers of cell adhesion and epithelial mesenchymal transformation, were significantly reduced. The levels of superoxide dismutase and lactate dehydrogenase decreased gradually, while the levels of glutathione, malondialdehyde and intracellular and extracellular ROS increased significantly. At the same time, LYY-35 induced increased apoptosis, increased expression of Bax, cleaved caspase3, cleaved PARP1, and decreased expression of Bcl-xl, which blocked the cell cycle to G0/G1 phase. The expressions of cell cycle checkpoint proteins Cyclin B1, Cyclin E1, CDK6, PCNA and PICH were significantly decreased. With the increase of LYY-35 concentration, the trailing phenomenon was more obvious in single cell gel electrophoresis. DNA damage repair proteins: BLM, BRCA-1 and PARP-1 expression decreased gradually.LYY-35 can inhibit the proliferation of non-small cell lung cancer A549 cells, block cell cycle, promote apoptosis, increase ROS production, cause DNA damage and interfere with DNA replication. LYY-35 is promising for the treatment of non-small cell lung cancer in the future.
摘要：
尽管fangchinoline已被广泛用作各种炎症和癌症疾病的辅助疗法，其对肿瘤细胞的作用机制尚不清楚。Fangchinoline衍生物LYY-35减少了A549细胞的数量，变形的细胞形态和增加的细胞碎片。细胞活力显著降低,而相同浓度的LYY-35对正常肺上皮细胞BEAS-2B活力影响不大。此外,LYY-35还可以减少迁移，A549细胞的增殖和侵袭能力。β-连环蛋白的水平，ZO-1和ZEB-1蛋白，细胞粘附和上皮间质转化的生物标志物，显着减少。超氧化物歧化酶和乳酸脱氢酶水平逐渐下降，而谷胱甘肽的水平，丙二醛和细胞内和细胞外ROS显著增加。同时,LYY-35诱导细胞凋亡增加，Bax的表达增加，caspase3切割，PARP1切割，Bcl-xl表达降低，从而阻断细胞周期至G0/G1期。细胞周期检查点蛋白CyclinB1、CyclinE1、CDK6、PCNA和PICH的表达显著降低。随着LYY-35浓度的增加,拖尾现象在单细胞凝胶电泳中更为明显。DNA损伤修复蛋白:BLM,BRCA-1和PARP-1表达逐步下降。LYY-35可抑制非小细胞肺癌A549细胞的增殖,阻断细胞周期，促进细胞凋亡，增加ROS产量，导致DNA损伤并干扰DNA复制。LYY-35有望在未来治疗非小细胞肺癌。
