18β-Glycyrrhetinic Acid Suppresses Cell Proliferation through Inhibiting Thromboxane Synthase in Non-Small Cell Lung Cancer

• DOI: 10.1371/journal.pone.0093690
• Publication Date: 2014-04-02T18:53:24Z
• Authors: Run-Yue Huang; Yong-Liang Chu; Qing-Chun Huang; Xiu-Min Chen; Ze-Bo Jiang; Xian Zhang; Xing Zeng
• Keywords: 0303 health sciences; Lung Neoplasms; Base Sequence; Science; Q; R; Real-Time Polymerase Chain Reaction; Small Cell Lung Carcinoma; 3. Good health; Immunoenzyme Techniques; 03 medical and health sciences; Cell Line, Tumor; Medicine; Glycyrrhetinic Acid; Humans; Thromboxane-A Synthase; RNA, Small Interfering; Research Article; Cell Proliferation; DNA Primers

18β-Glycyrrhetinic acid (18β-GA) is a bioactive component of licorice. The anti-cancer activity of 18β-GA has been studied in many cancer types, whereas its effects in lung cancer remain largely unknown. We first showed that 18β-GA effectively suppressed cell proliferation and inhibited expression as well as activity of thromboxane synthase (TxAS) in non-small cell lung cancer (NSCLC) cells A549 and NCI-H460. In addition, the administration of 18β-GA did not have any additional inhibitory effect on the decrease of cell proliferation induced by transfection with TxAS small interference RNA (siRNA). Moreover, 18β-GA failed to inhibit cell proliferation in the immortalized human bronchial epithelial cells 16HBE-T and another NSCLC cell line NCI-H23, both of which expressed minimal level of TxAS as compared to A549 and NCI-H460. However, 18β-GA abolished the enhancement of cell proliferation induced by transfection of NCI-H23 with pCMV6-TxAS plasmid. Further study found that the activation of both extracellular signal-regulated kinase (ERK)1/2 and cyclic adenosine monophosphate response element binding protein (CREB) induced by TxAS cDNA transfection could be totally blocked by 18β-GA. Altogether, we have delineated that, through inhibiting TxAS and its initiated ERK/CREB signaling, 18β-GA suppresses NSCLC cell proliferation. Our study has highlighted the significance of 18β-GA with respect to prevention and treatment of NSCLC.