# Brazilin Inhibits the Proliferation of Non‐Small Cell Lung Cancer by Regulating the STING/TBK1/IRF3 Pathway

## TL;DR

Brazilin, a natural compound, inhibits the growth of non-small cell lung cancer by activating a key immune-related pathway and causing cell death.

## Contribution

This study reveals Brazilin's novel anti-cancer mechanism via the STING/TBK1/IRF3 pathway in NSCLC.

## Key findings

- Brazilin reduces NSCLC cell proliferation and induces apoptosis and G2 cell cycle arrest.
- It activates the STING pathway and increases expression of CXCL10, CXCL9, and CCL5.
- STING inhibition reverses Brazilin's anti-tumor effects, confirming its role in the mechanism.

## Abstract

Non‐small cell lung cancer (NSCLC) stands as a predominant cause of cancer‐related mortality worldwide. Brazilin, an active isoflavonoid compound derived from Chinese herbs, has displayed anti‐cancer properties across various cancer cell lines. However, the precise anti‐tumour mechanism of Brazilin in NSCLC remains incompletely understood. In this paper, we demonstrated that Brazilin treatment significantly reduced the proliferation of NSCLC cells and induced apoptosis. Additionally, Brazilin caused G2 cell cycle arrest in NSCLC cells, characterised by decreased expression of Cyclin B1 and increased expression of P21. Brazilin also induced mitochondrial dysfunction and ROS production in NSCLC cells. Mechanistically, Brazilin treatment significantly activated the STING pathway and upregulated the expression of CXCL10, CXCL9, and CCL5 in NSCLC cell lines. Notably, the inhibition of the STING pathway with H‐151 enhances cell viability, suggesting STING is involved in Brazilin‐induced apoptosis. These findings underscore Brazilin as a promising anti‐cancer agent for NSCLC.