Xanthohumol inhibits the extracellular signal regulated kinase (ERK) signalling pathway and suppresses cell growth of lung adenocarcinoma cells.
Aberrant activation of the Ras/MEK/ERK signaling pathway has been frequently observed in non-small-cell lung carcinoma (NSCLC) and its important role in cancer progression and malignant transformation has been documented. Hence, the ERK1/2 kinase cascade becomes a potential molecular target in cancer treatment. Xanthohumol (XN, a prenylated chalcone derived from hope cones) is known to possess a broad spectrum of chemopreventive and anticancer activities. In our studies, the MTT and BrdU assays revealed that XN demonstrated greater antiproliferative activity against A549 lung adenocarcinoma cells than against the lung adenocarcinoma H1563 cell line. We observed that XN was able to suppress the activities of ERK1/2 and p90RSK kinases, followed by inhibition of phosphorylation and activation of the CREB protein. Additionally, the XN treatment of the cancer cells caused upregulation of key cell cycle regulators p53 and p21 as well as downregulation of cyclin D1. As a result, the cytotoxic effect of XN was attributed to the cell cycle arrest at G1 phase and induction of apoptosis indicated by increased caspase-3 activity. Thus, XN might be a promising anticancer drug candidate against lung carcinomas.
Department of Cell Biology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland. Electronic address: adrianna.slawinska-brych@poczta.umcs.lublin.pl.
Adrianna
A
Sławińska-Brych
Department of Virology and Immunology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland.
Barbara
B
Zdzisińska
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland.
Magdalena
M
Dmoszyńska-Graniczka
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland.
Witold
W
Jeleniewicz
Department of Medical Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland.
Jacek
J
Kurzepa
Department of Cell Biology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland.
Mariusz
M
Gagoś
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland.
Andrzej
A
Stepulak
D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D011427:Propiophenones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005419:Flavonoids; D011427:Propiophenones; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; C104536:xanthohumol
Apoptosis; CREB; Cell cycle; ERK1/2; NSLC; Xanthohumol