Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB194

Poster Communications

The effect of R547, a cyclin dependent kinase inhibitor, on hepatocellular carcinoma cell death

S. Kabadere1, B. Hacioglu1, G. Kus2

1. Department of Physiology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey. 2. Department of Health Programme, Open Faculty, Anadolu University, Eskisehir, Turkey.

Cancer is a disease that has high mortality rate in the world. Hepatocellular carcinoma (HCC) is derived from hepatocytes and it is the 3rd cause of cancer related death type. Therefore, there are many studies about developing new drugs and new therapy methods. Cyclin- dependent kinases (CDKs) and their cyclin partners regulate the cell cycle and check points. Since deregulation of CDKs is found with high frequency in many human cancer cells, inhibition of CDKs gives some guiding ideas for cancer studies (1, 2). In this study, we aimed to determine the possible effect of R547 which is a member of CDKs inhibitor family, on the growth and apoptosis of Hep G2, derived from human and H4IIE, derived from rat HCC. Both cell lines were exposed to 0,1, 1, 10, 50, 100 µM of R547 for 24 and 48 hours. We determined in vitro survival rate with MTT assay, apoptosis with flow cytometry, statistical significance by one way analysis of variance followed by Tukey's multiple comparison tests. Cisplatin was used as a positive control. At least three independent experiments were carried out for each group. At 0.1, 1, 10, 50, 100 µM doses of R547, the corresponding percentages of live Hep G2 cells were 101, 94, 93, 89 and %79 (p<0.001), respectively after 24 hours. The corresponding percentages of alive Hep G2 cells were 92, 101, 53.6 (p<0.01), 47.4 (p<0.001), and 41 (p<0.001) %, respectively, for 48 hours. After 24 hours culturing at the same doses of R547, the corresponding percentages of live H-4-IIE cells were 90, 80 (p<0.01), 63 (p<0.001), 47 (p<0.001) and 43 (p<0.001) % respectively. The corresponding percentages of alive H4IIE cells were 96, 85 (p<0.01), 46 (p<0.001), 44 (p<0.001) and 45 (p<0.01) %, respectively, for 48 hours. Because R547 was not affect the cell survival of Hep G2 cells for 24 hours, flow cytometry experiments were continued with H4IIE cells. The rates of early apoptotic H-4-IIE cells were about 38 and 45 (p<0.05 for both) % after applications of 10 and 25 μM R547 after 24 hours (control: 4.1%), respectively. According to our results, it is clear that R547 has stronger growth inhibitory action when compared to cisplatin. Additionally, R547 has apoptotic effect on H-4-IIE cells for 24 hours.

Where applicable, experiments conform with Society ethical requirements