RRC ID 67851
著者 Yahagi H, Yahagi T, Matsumura M, Igarashi K, Yokoyama N, Matsuzaki K.
タイトル Inhibitory activity of flavonoids from Ephedrae Herba on hypoxia signaling in PANC-1 cells and the evaluation of their mechanisms.
ジャーナル J Nat Med
Abstract 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.
巻・号 75(3)
ページ 612-622
公開日 2021-6-1
DOI 10.1007/s11418-021-01507-z
PII 10.1007/s11418-021-01507-z
PMID 33813664
MeSH Antineoplastic Agents / pharmacology* Cell Hypoxia / drug effects* Cell Line, Tumor Ephedra / chemistry* Flavonoids / pharmacology* Glucose Transporter Type 1 / metabolism Glycosides / chemistry Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Molecular Structure Pancreatic Neoplasms / metabolism* Phytochemicals / pharmacology RNA, Messenger / metabolism Signal Transduction / drug effects*
IF 2.055
リソース情報
ヒト・動物細胞 PANC-1(RCB2095)