Sinensetin Induces Oxidative Stress-Mediated Apoptosis in Non-Small Cell Lung Cancer Cells by Suppressing Nrf2/ARE-Dependent Antioxidant Defense.
- 1Center of Geriatric Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
- 2Department of Otolaryngology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
- 3Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
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.
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BibTeX
@article{li2026sinensetin,
title = {{Sinensetin Induces Oxidative Stress-Mediated Apoptosis in Non-Small Cell Lung Cancer Cells by Suppressing Nrf2/ARE-Dependent Antioxidant Defense.}},
author = {Junyan Li and Ruoyun He and Jiake He and Jian Ye and Yu Xie and Binfan Yuan},
journal = {Journal of biochemical and molecular toxicology},
year = {2026},
month = oct,
doi = {10.1002/jbt.71139},
url = {https://europepmc.org/article/MED/42927620},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sinensetin Induces Oxidative Stress-Mediated Apoptosis in Non-Small Cell Lung Cancer Cells by Suppressing Nrf2/ARE-Dependent Antioxidant Defense.
AU - Junyan Li
AU - Ruoyun He
AU - Jiake He
AU - Jian Ye
AU - Yu Xie
AU - Binfan Yuan
PY - 2026
DA - 2026/10/30
JO - Journal of biochemical and molecular toxicology
DO - 10.1002/jbt.71139
UR - https://europepmc.org/article/MED/42927620
AB - 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.
SN - 1095-6670
SN - 1099-0461
ER -