PT  - JOURNAL ARTICLE
AU  - SATOSHI OWADA
AU  - HITOSHI ENDO
AU  - CHISA OKADA
AU  - KAZUHIRO YOSHIDA
AU  - YUKARI SHIDA
AU  - MASAYUKI TATEMICHI
TI  - Setanaxib as a Potent Hypoxia-specific Therapeutic Agent Against Liver Cancer
AID  - 10.21873/anticanres.14510
DP  - 2020 Sep 01
TA  - Anticancer Research
PG  - 5071--5079
VI  - 40
IP  - 9
4099  - http://ar.iiarjournals.org/content/40/9/5071.short
4100  - http://ar.iiarjournals.org/content/40/9/5071.full
SO  - Anticancer Res2020 Sep 01; 40
AB  - Background/Aim: Liver cancer has extremely poor prognosis. The cancerous tissues contain hypoxic regions, and the available drugs are poorly effective in hypoxic environments. NADPH oxidase 4 (NOX4), producing reactive oxygen species (ROS), may contribute to cancer malignancy under hypoxic conditions. However, its role in liver cancer has not been examined in detail. Our aim was to explore the effects of setanaxib, a recently developed selective NOX4 inhibitor, in liver cancer cells under hypoxic conditions. Materials and Methods: Liver cancer cell lines (HepG2, HLE and Alexander) were treated with hypoxia-mimetic agent cobalt chloride. Cytotoxicity assays, immunoblot analysis and ROS detection assay were performed to detect the effect of setanaxib under hypoxic conditions. Results: Setanaxib exhibited hypoxia-selective cytotoxicity and triggered apoptosis in cancer cells. Moreover, setanaxib caused mitochondrial ROS accumulation under hypoxic conditions. Treatment with antioxidants markedly attenuated setanaxib-induced cytotoxicity and apoptosis under hypoxic conditions. Conclusion: Setanaxib caused mitochondrial ROS accumulation in a hypoxia-selective manner and evoked cancer cell cytotoxicity by inducing apoptosis. Thus, setanaxib has a great potential as a novel anticancer compound under hypoxic conditions.