Xanthohumol inhibits the extracellular signal regulated kinase (ERK) signalling pathway and suppresses cell growth of lung adenocarcinoma cells

• DOI: 10.1016/j.tox.2016.06.008
• Publication Date: 2016-06-18T21:17:18Z
• Authors: Adrianna Sławińsk...; Barbara Zdzisińska; Magdalena Dmoszyń...; Witold Jeleniewicz; Jacek Kurzepa; Mariusz Gagoś; Andrzej Stepulak
• Keywords: Cyclin-Dependent Kinase Inhibitor p21; Flavonoids; 0301 basic medicine; Propiophenones; 0303 health sciences; Lung Neoplasms; Caspase 3; MAP Kinase Signaling System; Down-Regulation; Adenocarcinoma of Lung; Antineoplastic Agents; Apoptosis; Adenocarcinoma; G1 Phase Cell Cycle Checkpoints; Up-Regulation; 3. Good health; 03 medical and health sciences; A549 Cells; Cell Line, Tumor; Humans; Cyclin D1; Tumor Suppressor Protein p53; Extracellular Signal-Regulated MAP Kinases; Signal Transduction

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.