Activity of ladanein on leukemia cell lines and its occurrence in Marrubium vulgare.
Three methoxylated flavones isolated from Marrubium peregrinum - ladanein, scutellarein-5,7,4'-trimethyl ether, and scutellarein-5,6,7,4'-tetramethyl ether - were assayed for their cytotoxicity towards a recently developed dasatinib-resistant murine leukemia cell line (DA1-3b/M2 (BCR-ABL)), together with the structurally related non-methylated flavone scutellarein. The most active compound, ladanein, was looked for in 20 common Lamiaceae species by a quick HPLC screening. Among the possible positive results, the most interesting source was found to be Marrubium vulgare, which led to the isolation and identification of ladanein for the first time in this species. Ladanein also displayed moderate (20-40 microM) activities against K562, K562R (imatinib-resistant), and 697 human leukemia cell lines but was toxic neither to MOLM13 nor to human peripheral blood mononuclear cells. This work provides a common natural source for the hemi-synthesis of future ladanein-derived flavones and the study of their antileukemic activity.
Alkhatib
Racha
R
Laboratoire de Pharmacognosie, Faculté des Sciences Pharmaceutiques et Biologiques, Université Lille Nord de France, Lille, France.
Joha
Sami
S
Cheok
Meyling
M
Roumy
Vincent
V
Idziorek
Thierry
T
Preudhomme
Claude
C
Quesnel
Bruno
B
Sahpaz
Sevser
S
Bailleul
François
F
Hennebelle
Thierry
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D047309:Flavones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D027522:Marrubium / Q000737:chemistry*; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D010936:Plant Extracts; C549432:ladanein