Abstract
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.
Highlights
The herbs used in traditional medicines provide a rich reservoir for extracting biologically active compounds
extracellular signal-regulated kinase (ERK)/cyclic adenosine monophosphate response element binding protein (CREB) signaling was involved in 18b-glycyrrhetinic acid (18b-GA) effects In our previous studies, we demonstrated that the activation of both ERK and CREB can be inhibited by thromboxane synthase (TxAS) inhibitors or thromboxane receptor (TP) antagonists, and activation of CREB is suppressed by specific ERK inhibitor [11,16]
This study demonstrated the tumor-suppressing effect of 18b-GA in non-small cell lung cancer (NSCLC) cells, and TxAS was found to be implicated in this effect
Summary
The herbs used in traditional medicines provide a rich reservoir for extracting biologically active compounds. Chemopreventive potential of 18b-GA has been documented in many types of cancer cells, such as human epithelial ovarian carcinoma, breast cancer and glioblastoma [5,6,7], little is known about the effects of 18b-GA in lung tumor growth. TxAS has been observed to be over-expressed in NSCLC specimens, as compared to normal lung tissues [9,10,11]. We report here that 18b-GA could suppress cell proliferation and induce apoptosis in NSCLC cells through, at least in part, inhibiting TxAS expression and activity. Such effects might be expected to be of considerable clinical relevance
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