TY - JOUR
AU - Matsuzaki, Keiichi
AB - Pancreatic cancer is a lethal disease with a very poor prognosis. Recent reports indicate that hypoxia signaling mediated by hypoxia-inducible factor (HIF) contributes to the progression of pancreatic cancer. Therefore, elucidating the inhibitor of hypoxia signaling may lead to the development of a candidate for new anticancer agents. During our screening program for HIF inhibitor from crude drug extracts, new acylated kaempferol glycosides, kaempferol 3-O-[4″-(E)-p-coumaroyl-3″-O-dihydroxypalmityl] rhamnoside (1) and kaempferol 3-O-[4″-(E)-p-coumaroyl-2″-O-dihydroxypalmityl] rhamnoside (2), were isolated from an acetone extract of Ephedrae Herba, together with eight known flavonol glycosides (3–10). The structures of novel compounds 1 and 2 were elucidated based on spectroscopic and chemical analyses. Using a cell-based HRE-driven luciferase reporter assay in a PANC-1 pancreatic cancer cell line, we found that these compounds demonstrated potent inhibitory activity on hypoxia signaling with IC50 values of 18.0 ± 0.6 and 13.3 ± 2.2 µM, respectively. Mechanistically, 2 reduced the amount of HIF-1α protein in the nuclear at 30 µM via the ubiquitin–proteasome pathway with no effect on the nuclear translocation of HIF proteins from cytosol and subsequently decreased Glut1 mRNA. These results indicate that 2 inhibits hypoxia signaling through a mechanism involving the reduction of HIF-1α protein levels and Glut1 mRNA and may have anti-pancreatic cancer effects.
TI - Inhibitory activity of flavonoids from Ephedrae Herba on hypoxia signaling in PANC-1 cells and the evaluation of their mechanisms
JF - Journal of Natural Medicines
DO - 10.1007/s11418-021-01507-z
DA - 2021-04-04
UR - https://www.deepdyve.com/lp/springer-journals/inhibitory-activity-of-flavonoids-from-ephedrae-herba-on-hypoxia-EiGSyZAjQM
SP - 612
EP - 622
VL - 75
IS - 3
DP - DeepDyve
ER -