Purpose: The aim of this study is to investigate the apoptotic
effect of a novel anti-cancer drug, ceranib-2 and impact on HIF-1α levels on
Methods: The cell line was treated in vitro with 0,1, 1, 5,
10, 25 and 50 µM ceranib-2 for 24 and 48 hours and cell viabilitiy was determined.
levels of acid ceramidase, caspase-3, caspase-8, caspase-9,
Cyc1, HIF-1α and TNF-α were measured by qPCR.
Results: Ceranib-2 at 10 µM
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 µM concentration. Caspase-9 mRNA levels did not differ after
24 and 48 hours. Ceranib-2 at 10 µM concentration lowered mRNA level of
Cyc1 against the control group after the 24- hour treatment. ASAH mRNA level was
reduced after the 48-hour treatment with 10 µM ceranib-2. Reduction of ASAH indicated
that 10 µM ceranib-2 could inhibit ceramidase after 48 hours and this may elavate
ceramide concentration. TNF-α mRNA increased after 24 and 48 hours, but HIF-1α
expression was low after 24 hours when compared to the control group. We
observed that ceranib-2 inhibits HIF-1α expression which might induce apoptosis
by reducing viability of HepG2 cells via ceranib-2.
Conclusion: We have found that ceranib-2 induces apoptosis in HepG2,
thus ceranib-2 may play an anti-cancer role at 10 µM