Involvement of p21WAF1/CIP1, pRB, Bax and NF-kappaB in induction of growth arrest and apoptosis by resveratrol in human lung carcinoma A549 cells.
Resveratrol, a polyphenolic phytoalexin found in grapes, may have the potential for prevention and therapy for human cancer. We report here that resveratrol inhibits the growth of human lung carcinoma A549 cells and provides molecular understanding of this effect. Resveratrol treatment of A549 cells resulted in a concentration-dependent induction of S phase arrest in cell cycle progression. This anti-proliferative effect of resveratrol was associated with a marked inhibition of the phosphorylation of the retinoblastoma protein (pRB) and concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP, which appears to be transcriptionally upregulated and is p53- dependent. In addition, resveratrol treatment resulted in induction of apoptosis as determined by fluorescence microscopy and flow cytometric analysis. These effects were found to correlate with an activation of caspase-3 and a shift in Bax/Bcl-xL ratio more towards apoptosis. Resveratrol treatment also inhibited the transcriptional activity of nuclear transcription factor kappaB (NF-kappaB). Taken together, these findings suggest that resveratrol has strong potential for development as an agent for prevention against human lung cancer.
Kim
Young-Ae
YA
Department of Biochemistry, Dongeui University College of Oriental Medicine and Research Institute of Oriental Medicine, Busan 614-052, Korea. choiyh@dongeui.ac.kr
Lee
Won Ho
WH
Choi
Tae Hyun
TH
Rhee
Sook-Hee
SH
Park
Kun-Young
KY
Choi
Yung Hyun
YH
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D016923:Cell Death; D002455:Cell Division; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D000077185:Resveratrol; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016196:S Phase; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077185:Resveratrol