Abstract

Licochalcone A (LicA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, has wide spectrum of pharmacological activities. In this study, the anti-cancer effects and potential mechanisms of LicA in non-small cell lung cancer (NSCLC) cells were studied. LicA decreased cell viability and induced apoptosis in a dose-dependent manner in NSCLC cells. LicA inhibited lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LicA treatment decreased the expression of MDM2, Cyclin B1, Cdc2 and Cdc25C in H460 and A549 cancer cell lines. In addition, LicA induced caspase-3 activation and poly-ADP-ribose polymerase (PARP) cleavage, which displayed features of apoptotic signals. Furthermore, LicA increased the expression of endoplasmic reticulum (ER) stress related proteins, such as p-EIF2α and ATF4. These data provide evidence that LicA has the potential to be used in the treatment of lung cancer.

Highlights

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide [1]

  • We found that piperlongumine, a natural alkaloid isolated from the fruit of long pepper, selectively kills gastric cancer cells while sparing their normal counterparts [13]

  • To determine whether the growth inhibition of lung cancer cells by Licochalcone A (LicA) was caused by cell cycle arresTto, tdweotelrumnignecawncheerthceelrl tlhineesgrwoewrtehtrienahtiebditwiointhovf alurinoguscaconncecerncterlalstiobnysLoifcALicwAafsocra1u6sehd, tbhyencethlle ccyeclllecayrcrleeswt, atswdoeltuernmgicnaendcbery cfelollwlincyetsowmeerteryt.rTeahteedrewsuiltths vinarFioiguusreco2nAc–e2nCtrasthioonwsedofthLaictALifcoAr 1d6oshe,thdeenpetnhdeecnetlllycyincdleuwceads Gde2t/eMrmarinreesdt binytflhoewtwcoytloumngetcrayn. cTehrecreellssu. lts in Figure 2A–C showed that LicA dose-dependently induced G2/M arrest in the two lung cancer cells

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Summary

Introduction

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide [1]. We clarified that two curcumin analogues selectively kill gastric cancer cells via activating ER stress pathway [14,15]. LicA E2f.feRcetsivueltlsy Suppressed the Proliferation of Human Lung Cancer Cells. LicA Induced G2/M Cell Cycle Arrest in Human Lung Cancer Cells. To determine whether the growth inhibition of lung cancer cells by LicA was caused by cell cycle arresTto, tdweotelrumnignecawncheerthceelrl tlhineesgrwoewrtehtrienahtiebditwiointhovf alurinoguscaconncecerncterlalstiobnysLoifcALicwAafsocra1u6sehd, tbhyencethlle ccyeclllecayrcrleeswt, atswdoeltuernmgicnaendcbery cfelollwlincyetsowmeerteryt.rTeahteedrewsuiltths vinarFioiguusreco2nAc–e2nCtrasthioonwsedofthLaictALifcoAr 1d6oshe,thdeenpetnhdeecnetlllycyincdleuwceads Gde2t/eMrmarinreesdt binytflhoewtwcoytloumngetcrayn. LLiiccAA iinndduucceess aappooppttoossiiss iinn hhuummaann lluunngg ccaanncceerr cceellllss.. All images shown here are representative of three independent experiments with similar results

Discussion
Cell Culture and Reagents
Cell Viability Assay
Cell Cycle Analysis
Cell Apoptosis Analysis
Western Blot Assay
Statistical Analysis
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