Ceranib-2 inhibits HIF1-α gene expression and induces apoptosis in HepG2 cells

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Özyurt R., Erkasap N., Özkurt M., Meral Eviş C. C., Karadağ A.

Çukurova Medical Journal, vol.45, no.4, pp.1318-1325, 2020 (ESCI)

  • Publication Type: Article / Article
  • Volume: 45 Issue: 4
  • Publication Date: 2020
  • Doi Number: 10.17826/cumj.702020
  • Journal Name: Çukurova Medical Journal
  • Journal Indexes: Emerging Sources Citation Index (ESCI), Academic Search Premier, Directory of Open Access Journals, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.1318-1325
  • Kütahya Health Sciences University Affiliated: Yes


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 HepG2.

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. mRNA 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 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 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 concentration.