Wikyungtang inhibits proliferation of A549 human lung cancer cells via inducing apoptosis and suppressing cyclooxygenase-2 activity.
Wikyungtang, an oriental herbal formulation, has been known to exert anti-inflammatory and anti-tumoral activity. However, its molecular mechanism of action is not understood. The purpose of the present study was to examine the effect of the water extract of Wikyungtang (WKT) on the growth of A549 human lung cancer cells. Treatment with WKT resulted in a dose-dependent growth inhibition coupled with the characteristic morphological features of apoptosis. Apoptosis-inducing concentrations of WKT induced caspase-3 and caspase-9 activation accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase and phospholipase C-gamma1. In addition, WKT-induced apoptosis in A549 cells was associated with a decreased expression of the anti-apototic Bcl-XL expression. WKT treatment also inhibited the expression of cyclooxygenase (COX)-2 and the accumulation of prostaglandin E2 without significant changes in the levels of COX-1. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of WKT.
Park
Dong Il
DI
Department of Oriental Medicine, Dongeui University College of Oriental Medicine, Busan 614-052, Korea. choiyh@dongeui.ac.kr
Choi
Hae-Yun
HY
Kam
Chul Woo
CW
Park
Cheol
C
Choi
Tae Hyun
TH
Lee
Won Ho
WH
Choi
Yung Hyun
YH
D000199:Actins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008565:Membrane Proteins; D051966:Phospholipase C gamma; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D000199:Actins; D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D010936:Plant Extracts; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C493316:Wikyungtang; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases