Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity

Oncology Reports
Ke Si WangXuejun Jin

Abstract

Hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that mediates the adaptation of tumor cells and tissues to the hypoxic microenvironment, has attracted considerable interest as a potential therapeutic target. Kamebakaurin is a diterpenoid compound isolated from Isodon excia (Maxin.) Hara, which has been used for anti-inflammatory activities. However, its antitumor activity along with molecular mechanism has not been reported. Kamebakaurin showed potent inhibitory activity against HIF-1 activation induced by hypoxia or CoCl2 in various human cancer cell lines. This compound significantly decreased the hypoxia-induced accumulation of HIF-1α protein, whereas it did not affect the expression of topoisomerase-I (Topo-I). Further analysis revealed that kamebakaurin inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. Furthermore, kamebakaurin prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). However, kamebakaurin caused cell growth inhibition via cell cycle arrest at G1 phase in tumor cells. In vivo studies, we further confirmed the inhibitory effect of kamebak...Continue Reading

References

Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
Jan 20, 1995·The Journal of Biological Chemistry·G L Wang, G L Semenza
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·P H MaxwellP J Ratcliffe
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Jul 10, 2004·Planta medica·Jeong-Hyung LeeJune Joon Lee
Apr 19, 2007·Cancer Metastasis Reviews·Peter Vaupel, Arnulf Mayer
Nov 21, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·M Christiane Brahimi-HornJacques Pouysségur
Feb 9, 2008·Cell Death and Differentiation·E B Rankin, A J Giaccia
May 27, 2008·Nature Reviews. Cancer·Mark W DewhirstBenjamin Moeller
Jun 3, 2008·Carcinogenesis·Eric HervouetJosef Houstek
Dec 15, 2010·Advanced Drug Delivery Reviews·Michael K DanquahRam I Mahato
May 25, 2011·Nature Reviews. Cancer·William R Wilson, Michael P Hay
Jul 8, 2011·Nature Reviews. Cancer·Elizabeth A MusgroveRobert L Sutherland
Apr 3, 2012·Cell·Chi V Dang

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