Selective and Non-Selective Pharmacological Activation of Hypoxia-Inducible Factor Differentially Modulate Cancer Progression of Hepatocellular Carcinoma Cell Line HepG2

Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. 2021. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA-Cancer J. Clin. 71, 209–249. https://doi.org/10.3322/caac.21660

Article  CAS  PubMed  Google Scholar 

Wicks E.E., Semenza G.L. 2022. Hypoxia-inducible factors: Cancer progression and clinical translation. J. Clin. Invest. 132, e159839.https://doi.org/10.1172/jci159839

Wang, Jiang B.H., Rue E.A., Semenza G.L. 1995. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-pas heterodimer regulated by cellular oxygen tension. Proc. Natl. Acad. Sci. U. S. A. 92, 5510–5514. https://doi.org/10.1073/pnas.92.12.5510

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fiorini G., Schofield C.J. 2024. Biochemistry of the hypoxia-inducible factor hydroxylases. Curr. Opin. Chem. Biol. 79, 102428. https://doi.org/10.1016/j.cbpa.2024.102428

Article  CAS  PubMed  Google Scholar 

Méndez-Blanco C., Fernández-Palanca P., Fondevila F., González-Gallego J., Mauriz J.L. 2021. Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: A systematic review with meta-analysis. Ther. Adv. Med. Oncol. 13, 1758835920987071. https://doi.org/10.1177/1758835920987071

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jo H., Lee J., Jeon J., Kim S.Y., Chung J.I., Ko H.Y., Lee M., Yun M. 2020. The critical role of glucose deprivation in epithelial-mesenchymal transition in hepatocellular carcinoma under hypoxia. Sci. Rep. 10, 1538. https://doi.org/10.1038/s41598-020-58124-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Madsen C.D., Pedersen J.T., Venning F.A., Singh L.B., Moeendarbary E., Charras G., Cox T.R., Sahai E., Erler J.T. 2015. Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis. EMBO Rep. 16, 1394–1408. https://doi.org/10.15252/embr.201540107

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kung-Chun Chiu D., Pui-Wah Tse A., Law C.T., Ming-Jing Xu I., Lee D., Chen M., Kit-Ho Lai R., Wai-Hin Yuen V., Wing-Sum Cheu J., Wai-Hung Ho D., Wong C.M., Zhang H., Ng I.O., Chak-Lui Wong C. 2019. Hypoxia regulates the mitochondrial activity of hepatocellular carcinoma cells through HIF/HEY1/PINK1 pathway. Cell Death. Dis. 10, 934. https://doi.org/10.1038/s41419-019-2155-3

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang D., Li T., Li X., Zhang L., Sun L., He X., Zhong X., Jia D., Song L., Semenza Gregg L., Gao P., Zhang H. 2014. HIF-1-mediated suppression of acyl-Coa dehydrogenases and fatty acid oxidation is critical for cancer progression. Cell Rep. 8, 1930–1942. https://doi.org/10.1016/j.celrep.2014.08.028

Article  CAS  PubMed  Google Scholar 

Holden P., Nair L.S. 2019. Deferoxamine: an angiogenic and antioxidant molecule for tissue regeneration. Tissue Eng., Part B. 25, 461–470. https://doi.org/10.1089/ten.teb.2019.0111

Article  CAS  Google Scholar 

Chowdhury R., Candela-Lena J.I., Chan M.C., Greenald D.J., Yeoh K.K., Tian Y.M., McDonough M.A., Tumber A., Rose N.R., Conejo-Garcia A., Demetriades M., Mathavan S., Kawamura A., Lee M.K., van Eeden F., Pugh C.W., Ratcliffe P.J., Schofield C.J. 2013. Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases. ACS Chem. Biol. 8, 1488–1496. https://doi.org/10.1021/cb400088q

Article  CAS  PubMed  Google Scholar 

Chan M.C., Ilott N.E., Schödel J., Sims D., Tum-ber A., Lippl K., Mole D.R., Pugh C.W., Ratcliffe P.J., Ponting C.P., Schofield C.J. 2016. Tuning the transcriptional response to hypoxia by inhibiting hypoxia-inducible factor (HIF) prolyl and asparaginyl hydroxylases. J. Biol. Chem. 291, 20661–20673. https://doi.org/10.1074/jbc.M116.749291

Article  CAS  PubMed  PubMed Central  Google Scholar 

Su X., Xie Y., Zhang J., Li M., Zhang Q., Jin G., Liu F. 2022. HIF-α activation by the prolyl hydroxylase inhibitor roxadustat suppresses chemoresistant glioblastoma growth by inducing ferroptosis. Cell Death Dis. 13, 861. https://doi.org/10.1038/s41419-022-05304-8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dai Z.J., Gao J., Ma X.B., Yan K., Liu X.X., Kang H.F., Ji Z.Z., Guan H.T., Wang X.J. 2012. Up-regulation of hypoxia inducible factor-1α by cobalt chloride correlates with proliferation and apoptosis in PC-2 cells. J. Exp. Clin. Cancer Res. 31, 28. https://doi.org/10.1186/1756-9966-31-28

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sulser P., Pickel C., Günter J., Leissing T.M., Crean D., Schofield C.J., Wenger R.H., Scholz C.C. 2020. HIF hydroxylase inhibitors decrease cellular oxygen consumption depending on their selectivity. FASEB J. 34, 2344–2358. https://doi.org/10.1096/fj.201902240R

Article  CAS  PubMed  Google Scholar 

Fujita H., Hirose K., Sato M., Fujioka I., Fujita T., Aoki M., Takai Y. 2019. Metformin attenuates hypoxia-induced resistance to cisplatin in the HepG2 cell line. Oncol. Lett. 17, 2431−2440. https://doi.org/10.3892/ol.2018.9869

Article  CAS  PubMed  Google Scholar 

Liu-Smith F., Krasieva T.B., Liu J., Liu J., Meyskens F.L. Jr. 2016. Measuring redox status of melanoma cells. in Methods in M olecular Biology, pp. 1−8. https://doi.org/10.1007/7651_2016_352

Mu H., Yu G., Li H., Wang M., Cui Y., Zhang T., Song T., Liu C. 2021. Mild chronic hypoxia-induced HIF-2α interacts with c-Myc through competition with HIF-1α to induce hepatocellular carcinoma cell proliferation. Cell. Oncol. 44, 1151–1166. https://doi.org/10.1007/s13402-021-00625-w

Article  CAS  Google Scholar 

Minoves M., Hazane-Puch F., Moriondo G., Boutin-Paradis A., Lemarié E., Pépin J.L., Godin-Ribuot D., Briançon-Marjollet A. 2023. Differential impact of intermittent vs. sustained hypoxia on HIF-1, VEGF and proliferation of HepG2 cells. Int. J. Mol. Sci. 24, 6875.https://doi.org/10.3390/ijms24086875

Chan Y.Y., Chan M.C. 2022. Pharmacological activation of the HIF pathway exerts distinct proliferative effects in MDA-MB-231 and MCF7 cells. ChemistrySelect. 7, e202200698. https://doi.org/10.1002/slct.202200698

Article  CAS  Google Scholar 

Cao M.Q., You A.B., Cui W., Zhang S., Guo Z.G., Chen L., Zhu X.D., Zhang W., Zhu X.L., Guo H., Deng D.J., Sun H.C., Zhang T. 2020. Cross talk between oxidative stress and hypoxia via thioredoxin and HIF-2α drives metastasis of hepatocellular carcinoma. FASEB J. 34, 5892–5905. https://doi.org/10.1096/fj.202000082R

Article  CAS  PubMed  Google Scholar 

Hervouet E., Cízková A., Demont J., Vojtísková A., Pecina P., Franssen-van Hal N.L.W., Keijer J., Simonnet H., Ivánek R., Kmoch S., Godinot C., Houstek J. 2008. HIF and reactive oxygen species regulate oxidative phosphorylation in cancer. Carcinogenesis. 29, 1528–1537. https://doi.org/10.1093/carcin/bgn125

Article  CAS  PubMed  Google Scholar 

Wu Z., Wang H., Fang S., Xu C. 2018. Roles of endoplasmic reticulum stress and autophagy on H2O2‑induced oxidative stress injury in HepG2 cells. Mol. Med. Rep. 18, 4163–4174. https://doi.org/10.3892/mmr.2018.9443

Article  CAS  PubMed  PubMed Central  Google Scholar 

Saeki I., Yamamoto N., Yamasaki T., Takami T., Maeda M., Fujisawa K., Iwamoto T., Matsumoto T., Hidaka I., Ishikawa T., Uchida K., Tani K., Sakaida I. 2016. Effects of an oral iron chelator, deferasirox, on advanced hepatocellular carcinoma. World J. Gastroenterol. 22, 8967–8977. https://doi.org/10.3748/wjg.v22.i40.8967

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chan M.C., Atasoylu O., Hodson E., Tumber A., Leung I.K.H., Chowdhury R., Gómez-Pérez V., Demetriades M., Rydzik A.M., Holt-Martyn J., Tian Y.M., Bishop T., Claridge T. D.W., Kawamura A., Pugh C.W., Ratcliffe P.J., Schofield C.J. 2015. Potent and selective triazole-based inhibitors of the hypoxia-inducible factor prolyl-hydroxylases with activity in the murine brain. PLoS One 10, e0132004-e. https://doi.org/10.1371/journal.pone.0132004

Strocchi S., Reggiani F., Gobbi G., Ciarrocchi A., Sancisi V. 2022. The multifaceted role of EGLN family prolyl hydroxylases in cancer: Going beyond HIF regulation. Oncogene. 41, 3665–3679. https://doi.org/10.1038/s41388-022-02378-8

Article  CAS  PubMed  Google Scholar 

Yu M., Lun J., Zhang H., Zhu L., Zhang G., Fang J., 2021. The non-canonical functions of HIF prolyl hydroxylases and their dual roles in cancer. Int. J. Biochem. Cell Biol. 135, 105982. https://doi.org/10.1016/j.biocel.2021.105982

Article  CAS  PubMed  Google Scholar 

Liu Y., Liu Y., Yan X., Xu Y., Luo F., Ye J., Yan H., Yang X., Huang X., Zhang J., Ji G., 2014. Hifs enhance the migratory and neoplastic capacities of hepatocellular carcinoma cells by promoting EMT. Tumor Biol. 35, 8103–8114. .https://doi.org/10.1007/s13277-014-2056-0

Article  CAS 

Comments (0)

No login
gif