Prenylation enhances cytotoxicity of apigenin and liquiritigenin in rat H4IIE hepatoma and C6 glioma cells.
Antioxidative as well as cytotoxic effects of the prenylated flavonoids licoflavone C (8-prenylapigenin) and isobavachin (8-prenylliquiritigenin) were investigated in comparison to the corresponding non-prenylated flavonoids (apigenin, liquiritigenin) and vitexin (apigenin-C8-glucoside) using metabolically active H4IIE hepatoma and metabolically poorly active C6 glioma cells. None of the substances showed radical scavenging activities in the 2,2-diphenyl-1-picrylhydrazyl (DPPH)-assay nor were they effective in protection against H2O2-induced intracellular 2',7'-dichlorodihydrofluorescein (H2DCF) oxidation (fluorescent probe for oxidative stress) in H4IIE and C6 cells. When the intrinsic effects of the substances were investigated, licoflavone C and isobavachin exerted a pronounced toxicity in both H4IIE (IC50 values of 42+/-5 and 96+/-19 micromol/L) and C6 cells (IC50 values of 37+/-6 and 69+/-3 micromol/L) while the non-prenylated analogues as well as the glycosylated derivate vitexin showed almost no cytotoxic effect up to 250 micromol/L. In H4IIE cells the induction of apoptotic cell death by licoflavone C and icobavachin was detected as an activation of caspase 3/7 (6- and 3.3-fold, respectively). Based on these experiments we suggest that C8-prenylation of a flavonoid enhances the cytotoxicity inducing an apoptotic cell death in H4IIE cells without affecting antioxidative properties.
Wätjen
W
W
Institute of Toxicology, Heinrich-Heine-University, P.O. Box 101007, 40001 Düsseldorf, Germany. wim.waetjen@uni-duesseldorf.de
Weber
N
N
Lou
Y-j
YJ
Wang
Z-q
ZQ
Chovolou
Y
Y
Kampkötter
A
A
Kahl
R
R
Proksch
P
P
D000818:Animals; D047310:Apigenin / Q000494:pharmacology / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D044950:Flavanones / Q000633:toxicity*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D017368:Protein Prenylation; D051381:Rats
D044950:Flavanones; D005419:Flavonoids; C468753:isobavachin; D047310:Apigenin; C032731:vitexin; C083152:liquiritigenin