Document Type: Research Articles
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Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Neglected, Zoonosis and Vector-Borne Disease Group, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Cholangiocarcinoma Research Institue, Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen 40002, Thailand.
Department of Thai Traditional Medicine, Faculty of Natural Resources, Rajamangala University of Technology Isan Sakonnakhon Campus, Sakon Nakhon 47160, Thailand.
Department of Anesthesiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Faculty of Veterinary Medicine, Mahasarakham University, Maha Sarakham 44000, Thailand.
Program of Public Health, Faculty of Science and Technology, Loei Rajabhat University Khon Kaen Education Center, Khon Kaen 40000, Thailand.
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Aspirin and other non-steroidal anti-inflammatory drugs reduce the risk of cancer due to their anti-proliferative and apoptotic effects, which are the important mechanisms for their anti-tumor activity. Here, the effect of aspirin on human cholangiocarcinoma cells (KKU-214) and the underlying mechanisms of its action were explored. Cell proliferation was measured by sulforhodamine B (SRB) assay, while cell cycle distribution and apoptosis were determined by flow cytometry. Western blotting was used to explore protein expression underlying molecular mechanisms of anti-cancer treatment of aspirin. Aspirin reduced cell proliferation in a dose- and time-dependent manner, and altered the cell cycle phase distribution of KKU-214 cells by increasing the proportion of cells in the G0/G1 phase and reducing the proportion in the S and G2/M phases. Consistent with its effect on the cell cycle, aspirin also reduced the expression of cyclin D1 and cyclin-dependent kinase 4 (Cdk-4), which are important for G0/G1 cell cycle progression. Treatment with aspirin led to increased induction of apoptosis in a dose-dependent manner. Further analysis of the mechanism underlying the effect of this drug showed that aspirin induced the expression of the tumor-suppressor protein p53 while inhibiting the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2). Correspondingly, the activation of caspase-9 and -3 was also increased. These findings suggest that aspirin causes cell cycle arrest and apoptosis, both of which could contribute to its anti-proliferative effect.