Rengyolone inhibits apoptosis via etoposide-induced caspase downregulation.
In the course of screening for substances inhibiting apoptosis of U937 human leukemia cells induced by etoposide (10 microg/ml), Forsythiae fructus, which showed a high level of inhibition, was selected. The regulating compounds were purified from the ethyl acetate extract by silica gel column chromatography and HPLC. The active substance was purified and identified as rengyolone by spectroscopic methods. This compound showed inhibitory activity on caspase-3 induction, a major protease of the apoptosis cascade, with an IC50 value of 38.96 microM after 8 h of etoposide treatment in U937 cells. The expression level of caspase-3 and poly(ADP-ribose) polymerase (PARP) were dose-dependently inhibited by the compound, suggesting that rengyolone inhibits etoposide-induced apoptosis via downregulation of caspases.
Kim
Jin Hee
JH
Korea Research Institute of Bioscience and Biotechnology, 52 Eoun-dong, Yusong, Daejon 305-764, Korea.
Lee
Choong Hwan
CH
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis*; D061945:Caspase Inhibitors; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D010946:Plants, Medicinal / Q000737:chemistry; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D020298:U937 Cells
D000972:Antineoplastic Agents, Phytogenic; D061945:Caspase Inhibitors; D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; C509673:Rengyolone; D005047:Etoposide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3