Inhibitory Effect of Aspirin on Cholangiocarcinoma Cells

Document Type: Research Articles

Authors

1 Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

2 Neglected, Zoonosis and Vector-Borne Disease Group, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

3 Cholangiocarcinoma Research Institue, Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen 40002, Thailand.

4 Department of Thai Traditional Medicine, Faculty of Natural Resources, Rajamangala University of Technology Isan Sakonnakhon Campus, Sakon Nakhon 47160, Thailand.

5 Department of Anesthesiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

6 Faculty of Veterinary Medicine, Mahasarakham University, Maha Sarakham 44000, Thailand.

7 Program of Public Health, Faculty of Science and Technology, Loei Rajabhat University Khon Kaen Education Center, Khon Kaen 40000, Thailand.

8 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

Abstract

 
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.

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