Abstract:
Purpose: The aim of this study is to investigate the apoptotic effect of a novel anti-cancer drug, ceranib-2 and impact on HIF-1 alpha levels on HepG2.
Materials and Methods: The cell line was treated in vitro with 0,1, 1, 5, 10, 25 and 50 mu M ceranib-2 for 24 and 48 hours and cell viabilitiy was determined. mRNA levels of acid ceramidase, caspase-3, caspase-8, caspase-9, Cyc1, HIF-1 alpha and TNF-alpha were measured by qPCR.
Results: Ceranib-2 at 10 mu M concentration reduced the viability by about 58 % after 24 and 48 hours. The same dose increased mRNA level of caspase-3 and no change was detected on caspase-8 when compared to the control group after 24 hours. No difference was detected on caspase-3, but caspase-8 mRNA level increased after 48 hours with ceranib-2 at 10 mu M concentration. Caspase-9 mRNA levels did not differ after 24 and 48 hours. Ceranib2 at 10 mu M concentration lowered mRNA level of Cyc1 against the control group after the 24hour treatment. ASAH mRNA level was reduced after the 48-hour treatment with 10 mu M ceranib-2. Reduction of ASAH indicated that 10 mu M ceranib-2 could inhibit ceramidase after 48 hours and this may elavate ceramide concentration. TNF-alpha mRNA increased after 24 and 48 hours, but HIF-1 alpha expression was low after 24 hours when compared to the control group.
Conclusion: We have found that ceranib-2 induces apoptosis in HepG2, thus ceranib-2 may play an anticancer role at 10 mu M concentration.
