Work

Sinensetin Induces Oxidative Stress‐Mediated Apoptosis in Non‐Small Cell Lung Cancer Cells by Suppressing Nrf2/ARE‐Dependent Antioxidant Defense

Year: 2026

Type: article

Abstract: Non-small cell lung cancer (NSCLC) cells frequently depend on Nrf2/ARE-driven antioxidant programs to maintain redox balance and evade apoptosis. This study investigated whether sinensetin, a naturally occurring polymethoxylated flavone, reduces NSCLC cell survival by interfering with this cytoprotective pathway. A549 and H1299 NSCLC cells and normal BEAS-2B bronchial epithelial cells were exposed to sinensetin. Cell viability was measured by MTT assay, apoptosis was quantified by Annexin V-FITC/PI flow cytometry, and pathway- and apoptosis-related proteins were analyzed by western blotting. Nrf2 distribution was evaluated by nuclear/cytoplasmic fractionation, ARE-dependent transcription was assessed using a dual-luciferase reporter system, and Nrf2 was silenced by shRNA. Intracellular ROS was measured by DCFH-DA, antioxidant rescue was assessed with N-acetyl-l-cysteine (NAC), Nrf2/ARE-related proteins were examined in BEAS-2B cells, and Nrf2 overexpression was used as a rescue approach in A549 cells. Sinensetin inhibited NSCLC cell growth, increased apoptosis, reduced total and nuclear Nrf2, decreased ARE reporter activity, and downregulated HO-1 and NQO1. Sinensetin also increased intracellular ROS, whereas NAC partially reduced ROS accumulation, restored cell viability, and decreased apoptosis. BEAS-2B cells showed comparatively modest Nrf2/ARE pathway changes. Nrf2 overexpression partially restored HO-1 and NQO1, reduced apoptotic signaling, and attenuated sinensetin-induced loss of viability and apoptosis. These results support a model in which sinensetin promotes oxidative stress-mediated apoptosis in NSCLC cells, at least in part, through suppression of Nrf2/ARE-dependent antioxidant defense.

Source: Journal of Biochemical and Molecular Toxicology

DOI: 10.1002/jbt.71139

Authors: Junyan Li, Ruoyun He, Jiake He, Jian Ye, Yu Xie, Binfan Yuan

Institution: Guangdong Medical College

Language: English

Topic: Genomics, phytochemicals, and oxidative stress

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,020