Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human promyelocytic leukemia cells.
Extracts of the whole herb of Artemisia asiatica Nakai (Asteraceae) have been used in traditional oriental medicine for the treatment of inflammation, cancer and other disorders. In the present work, we have evaluated the apoptosis-inducing capability of eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone), a pharmacologically active ingredient of A. asiatica, in cultured human promyelocytic leukemia (HL-60) cells. Thus, eupatilin exhibited concentration-dependent inhibitory effects on viability and DNA synthesis capability of HL-60 cells. The anti-proliferative effect of eupatilin was attributable to its apoptosis-inducing activity as determined by characteristic nuclear condensation, in situ terminal end-labeling of fragmented DNA (TUNEL), release of mitochondrial cytochrome c into cytoplasm, proteolytic activation of caspases-9, -3, and -7, and cleavage of poly(ADP-ribose)polymerase. Eupatilin-induced HL-60 cell apoptosis does not appear to be mediated via alteration in Bcl-2/Bax-2. Taken together, the above findings suggest that eupatilin has chemopreventive and cytotoxic effects.
Seo
H J
HJ
College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-gu, 151-742, Seoul, South Korea.
Surh
Y J
YJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019306:Artemisia; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D003574:Cytochrome c Group; D005419:Flavonoids; D010936:Plant Extracts; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; C045325:eupatilin; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases