Abstract
Elements of the hypoxia inducible factor (HIF) transcriptional system, a key regulator of the cellular hypoxic response, are up-regulated in a range of cancer cells. HIF is fundamentally involved in tumor angiogenesis, invasion, and energy metabolism. Inhibition of the transcriptional activity of HIF may be of therapeutic benefit to cancer patients. We recently described the identification of two marine pyrroloiminoquinone alkaloids with potent activity in inhibiting the interaction between the oncogenic transcription factor HIF-1α and the coactivator protein p300. Herein, we present further characterization data for these two screening hits: discorhabdin H (1) and discorhabdin L (2), with a specific focus on their anti-angiogenic and anti-tumor effects. We demonstrated that only discorhabdin L (2) possesses excellent anti-angiogenic activity in inhibiting endothelial cell proliferation and tube formation, as well as decreasing microvessel outgrowth in the ex vivo rat aortic ring assay. We further showed that discorhabdin L (2) significantly inhibits in vivo prostate tumor growth in a LNCaP xenograft model. In conclusion, our findings suggest that discorhabdin L (2) represents a promising HIF-1α inhibitor worthy of further drug...Continue Reading
References
Feb 1, 2000·Biochemical and Biophysical Research Communications·E A KrugerW D Figg
Feb 2, 2002·Science·David LandoMurray L Whitelaw
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Sonja A DamesPeter E Wright
Apr 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Steven J FreedmanMichael J Eck
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Jul 21, 2004·Cancer Cell·Andrew L KungDavid M Livingston
Aug 31, 2004·Journal of Natural Products·Edith M AntunesMichael T Davies-Coleman
May 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Christina TherapontosNeil Vargesson
Jul 11, 2009·The Journal of Biological Chemistry·Kristina M CookChristopher J Schofield
May 19, 2010·Marine Drugs·Yasufumi WadaYasuyuki Kita
Jun 22, 2011·Chemical Reviews·Jin-Feng HuShi-Biao Wu
Apr 30, 2014·Molecular Cancer·Kelie M ReeceWilliam D Figg
Apr 22, 2015·Journal of the American Chemical Society·Susanna T S ChanKirk R Gustafson
May 4, 2016·Journal of Natural Products·Andrew K L GoeyWilliam D Figg
Aug 10, 2016·The Journal of Biological Chemistry·Mun Chiang ChanChristopher J Schofield
Citations
Jan 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Arnold Amusengeri, Özlem Tastan Bishop
Jan 19, 2019·Marine Drugs·Jarmo-Charles J KalinskiRosemary A Dorrington
Jan 24, 2019·International Journal of Molecular Sciences·Chloe-Anne MartinezKristina M Cook
Aug 6, 2020·Marine Drugs·Cary F C LamBrent R Copp
Jan 14, 2021·Marine Drugs·Fengjie LiDeniz Tasdemir
Feb 3, 2021·Marine Drugs·Jarmo-Charles J KalinskiRosemary A Dorrington
Oct 23, 2020·Clocks & Sleep·Monica N MorganKristina M Cook