Decrease of AIM2 mediated by luteolin contributes to non-small cell lung cancer treatment

Qian Yu,Shuwen Yue,Qidi Ying,Zhaoshi Bai,Xin Xie,Bending Tong,Lingman Ma,Minda Zhang,Qing Wei

doi:10.1038/s41419-019-1447-y

Abstract

Non-small cell lung cancer (NSCLC) is one of the most common malignancies in the world. Although extensive studies showed that luteolin exhibited antitumor effects against NSCLC, the mechanism has not been fully established. In the present study, we found that luteolin significantly reduced the expression of absent in melanoma 2 (AIM2) at both mRNA and protein levels leading to the suppression of AIM2 inflammasome activation, which induced G2/M phase arrest and inhibited epithelial–mesenchymal transition (EMT) in NSCLC. Furthermore, the inhibitory effects of luteolin on NSCLC cells were abolished by the knockdown of AIM2. On the contrary, the antitumor effects of luteolin could be notably reversed by the overexpression of AIM2. In addition, luteolin reduced poly(dA:dT)-induced caspase-1 activation and IL-1β cleavage in NSCLC cells. These findings suggested that AIM2 was essential to luteolin-mediated antitumor effects. The antitumor effects of luteolin, which were closely associated with AIM2, were also confirmed in the A549 and H460 xenograft mouse models. Collectively, our study displayed that the antitumor effects of luteolin on NSCLC were AIM2 dependent and the downregulation of AIM2 might be an effective way for NSCLC treatment.

Highlights

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains as a serious public health concern[1]
We indicated that luteolin suppressed the activation of absent in melanoma 2 (AIM2) inflammasome by the downregulation of AIM2, thereby inducing G2/M phase arrest and inhibiting epithelial–mesenchymal transition (EMT) in A549 and H460 cells
To determine the effect of luteolin on NSCLC cell growth, A549, H460, and H226 cells were treated with various concentrations of luteolin and cell inhibition rates were assessed by 3-(4,5-Dimethyl-2-thizolyl)-2,5

Summary

Introduction

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains as a serious public health concern[1]. Absent in melanoma 2 (AIM2), as a receptor for cytosolic dsDNA, combines apoptosis-associated speck-like protein containing a CARD (ASC) adaptor and procaspase-1 to form an AIM2 inflammasome[6,7]. This multiprotein complex senses host- and pathogen-associated cytoplasmic DNA and induces caspase-1 activation, resulting in proteolytic cleavage of the proinflammatory cytokines pro-IL-1β and pro-IL-18 to active forms[8,9,10]. AIM2 mRNA levels were significantly upregulated in oral squamous cell carcinoma and Epstein-Barr virus-induced nasopharyngeal carcinoma[11,12]. As previous study reported that the overexpression of AIM2 could promote AIM2

Methods

Results

Conclusion