ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2024; 15(13):4232-4243. doi:10.7150/jca.96582 This issue Cite
Research Paper
Derived from fangchinoline, LYY-35 exhibits an inhibiting effect on human NSCLC cancer A549 cells
1. Department of Immunology, Basic Medical College, Guizhou Medical University, Guiyang, 550025, China.
2. Oncology department, General Hospital of Hunan Medical College, Huaihua, 418000, China.
3. Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, 550002, China.
4. School of Pharmaceutical Sciences, Guizhou University, Guiyang, 550025, China.
5. Department of Oncology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100039, China.
6. State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, China.
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.
Keywords: LYY-35, A549, cell cycle, cell apoptosis, DNA damage
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