Antiproliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligand-mediated apoptotic pathway in human non-small cell lung cancer A549 cells.
1. Paeoniflorin (PF), isolated from the paeony root, is reported to have immunoregulatory, neuromuscular blocking, anticonvulsant, antihyperglycaemic and antihypotensive effects. 2. The present study investigated the antiproliferative activity of PF. The results showed that PF inhibited the proliferation of A549 by blocking cell cycle progression in the G(0)/G(1) phase and inducing apoptosis. 3. An ELISA showed that G(0)/G(1) phase arrest may be due to p53-independent induction of p21/wild-type p53-activated fragment 1 (WAF1). Increased protein expression of Fas/apoptosis-1 (APO-1) and its two ligands, membrane-bound Fas ligand and soluble Fas ligand, may be responsible for the PF-induced apoptosis. 4. This is the first study to show that the induction of p21/WAF1 and the activity of the Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of PF in A549 cells.
Hung
Jen-Yu
JY
Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Yang
Chih-Jen
CJ
Tsai
Ying-Ming
YM
Huang
Hurng-Wern
HW
Huang
Ming-Shyan
MS
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D039821:Monoterpenes; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*; D006027:Glycosides
D000972:Antineoplastic Agents, Phytogenic; D001565:Benzoates; D001952:Bridged-Ring Compounds; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053222:Fas Ligand Protein; D005960:Glucosides; D039821:Monoterpenes; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; C493956:CDKN1A protein, human; C495901:TP53 protein, human; C015423:peoniflorin; D006027:Glycosides