Gökhan KUŞ, Hatice Mehtap KUTLU, Betül HACIOĞLU, Selda KABADERE

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

Hepatocellular carcinoma (HCC) is the third main cause of cancer-related death. Cyclin-dependent kinases (CDKs) and theircyclin partners regulate the cell cycle. Since inhibition of CDKs gives some guiding ideas for cancer studies, we aimed to determine thepossible effects of R547, a cyclin kinase 1-2-4 inhibitor, on proliferation and apoptotic mechanisms of Hep G2 cells (human) and H-4-II-E cells derived from rat HCC. We determined in vitro survival rates with MTT assay, apoptosis with flow cytometry, morphologicalchanges with confocal microscopy, and ultrastructural changes by transmission electron microscopy. Cisplatin was used as a positivecontrol. After 24 h of culture with 0.1, 1, 10, 50, and 100 µM doses of R547, the corresponding percentages of live Hep G2 cells were101%, 94%, 93%, 89%, and 79% (P < 0.001), respectively. However, with the same R547 doses the live Hep G2 cell percentages were92%, 101%, 53.6% (P

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