Cytotoxicity of artesunic acid homo- and heterodimer molecules toward sensitive and multidrug-resistant CCRF-CEM leukemia cells.
A novel approach to circumvent multidrug resistance is hybridization of natural products in dimers. We analyzed homodimers of two artesunic acid molecules and heterohybrids of artesunic acid and betulin in human CCRF-CEM and multidrug-resistant P-glycoprotein-overexpressing CEM/ADR5000 leukemia cells. Multidrug-resistant cells were not cross-resistant to the novel compounds. Collateral sensitivity was observed for artesunic acid homodimer. Artesunic acid and artesunic acid homodimer induced G0/G1 cell cycle arrest, apoptosis, and formation of reactive oxygen species.
Horwedel
Cindy
C
Pharmaceutical Biology (C015), German Cancer Research Center, Heidelberg, Germany.
Tsogoeva
Svetlana B
SB
Wei
Shengwei
S
Efferth
Thomas
T
D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005562:Formazans; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D017382:Reactive Oxygen Species / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013386:Succinates / Q000737:chemistry / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D000094062:Betulinic Acid
D037621:Artemisinins; D005562:Formazans; D017382:Reactive Oxygen Species; D013386:Succinates; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid; C059088:1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan; C111789:artesunic acid