Combined effects of resveratrol and paclitaxel on lung cancer cells.
Resveratrol (3,4',5-trihydroxystilbene) is a phytoalexin found in grapes and other food products that can prevent cancer. We studied the in vitro biological activity of this compound by examining its effect on proliferation and inducing apoptosis in three lung cancer cell lines (A549, EBC-1, Lu65). Resveratrol inhibited the growth of A549, EBC-1 and Lu65 lung cancer cells by 50% (ED50) at concentrations between 5-10 microM. We also examined the combined effects in these cells of resveratrol and paclitaxel, an essential chemotherapeutic agent against lung cancer. Although simultaneous exposure to resveratrol plus paclitaxel did not result in significant synergy, resveratrol (10 microM, 3 days) significantly enhanced the subsequent antiproliferative effect of paclitaxel. In addition, resveratrol as well as paclitaxel induced apoptosis in EBC-1 and Lu65 cells, as measured by TUNEL and caspase assays, as well as flow cytometry. Resveratrol (10 microM, 3 days) similarly enhanced the subsequent apoptotic effects of paclitaxel. We examined the effects of resveratrol and paclitaxel on levels of p21waf1, p27kip1, E-cadherin, EGFR and Bcl-2 in EBC-1 cells. Resveratrol (10 microM, 3 days) prior to paclitaxel induced p21waf1 expression approximately 4-fold. These results suggest that resveratrol may be a promising alternative therapy for lung cancer and that lung cancer cells exposed to resveratrol have a lowered threshold for killing by paclitaxel.
Kubota
Tetsuya
T
Department of Medicine, Kochi Medical School, Kochi, 783-8505, Japan. kubotat@med.kochi-ms.ac.jp
Uemura
Yoshiki
Y
Kobayashi
Makoto
M
Taguchi
Hirokuni
H
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000096:biosynthesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis; D004334:Drug Administration Schedule; D004357:Drug Synergism; D066246:ErbB Receptors / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
C493956:CDKN1A protein, human; D015820:Cadherins; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D066246:ErbB Receptors; D020169:Caspases; D017239:Paclitaxel; D000077185:Resveratrol