Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human gastric cancer (AGS) cells.
Extracts of Artemisia asiatica Nakai (Asteraceae) possess anti-inflammatory and antioxidative activities. Eupatilin (5,7-dihydroxy-3',4', 6-trimethoxyflavone), one of the pharmacologically active ingredients derived from A. asiatica was shown to induce apoptosis in human promyelocytic leukemia (HL-60) cells. In the present study, we examined the ability of eupatilin to induce apoptosis in human gastric cancer (AGS) cells. Eupatilin induced the apoptosis of AGS cells as revealed by a decrease in the ratio of pro-apoptotic Bax and anti-apoptotic Bcl-2, as well as the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP). The pro-apoptotic effects of eupatilin were further verified by its perturbation of the mitochondrial transmembrane potential (DeltaPsim). In addition, eupatilin treatment led to an elevated expression of p53 and p21. Eupatilin inhibited the activation of ERK1/2 and Akt, which are important components of cell-survival pathways.
Kim
Min-Jung
MJ
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Seoul, South Korea.
Kim
Do-Hee
DH
Na
Hye-Kyung
HK
Oh
Tae Young
TY
Shin
Chang-Yell
CY
Surh Ph D Professor
Young-Joon
YJ
D017209:Apoptosis / Q000187:drug effects*; D019306:Artemisia; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C045325:eupatilin; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases