Distinct roles and molecular mechanisms of nicotine and benzo(a)pyrene in ferroptosis of lung adenocarcinoma and lung squamous cell carcinoma

Min G Wen ¹, Hui X Zheng ², Ying Z Zhao ²

⁰Department of Community Nursing, College of Nursing, Jinzhou Medical University, Jinzhou, People's Republic of China.

Tobacco Induced Diseases +

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July 1, 2024

View abstract on PubMed

Summary

Nicotine protects lung cancer cells from ferroptosis by increasing EGFR and SLC1A5, while benzo(a)pyrene induces ferroptosis via FDFT1. This study clarifies smoking

Area Of Science

Cellular Biology
Oncology
Biochemistry

Background

Ferroptosis, a cell death form driven by lipid peroxidation, is linked to iron metabolism and lung cancer development and resistance.
The precise mechanisms of smoking's impact on ferroptosis in lung cancer remain largely undefined.
Understanding these mechanisms is crucial for developing targeted therapies.

Purpose Of The Study

To identify ferroptosis-related gene signatures in lung cancer patients based on smoking status.
To investigate the roles of nicotine and benzo(a)pyrene (BaP) in ferroptosis of non-small-cell lung cancer (NSCLC) cells.

Main Methods

Secondary bioinformatics analysis of The Cancer Genome Atlas (TCGA) database to identify ferroptosis-related genes and establish signatures in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD).
Experimental cell culture analysis to examine the effects of nicotine and BaP on NSCLC cells.
Assessed reactive oxygen species (ROS) levels, glutathione peroxidase (GPX4) expression, epidermal growth factor receptor (EGFR), solute carrier one family member 5 (SLC1A5), and farnesyl diphosphate farnesyltransferase 1 (FDFT1).

Main Results

Nicotine inhibited ROS and upregulated GPX4, EGFR, and SLC1A5, protecting NSCLC cells from ferroptosis.
Benzo(a)pyrene (BaP) had opposite effects on ROS and GPX4, inducing ferroptosis in NSCLC cells dependent on FDFT1 expression.
Distinct ferroptosis-associated gene signatures were identified for LUSC and LUAD patients with different smoking statuses.

Conclusions

Nicotine confers protection against ferroptosis in LUAD and LUSC cells by enhancing EGFR and SLC1A5 expression.
BaP induces ferroptosis in these lung cancer cells, a process dependent on FDFT1 expression.
This research elucidates differential roles of major smoking components in ferroptosis, providing insights into lung cancer progression and treatment resistance.

Keywords:

GPX4 benzo(a)pyrene ferroptosis nicotine non-small cell lung cancer

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