Lycopene Protects against Smoking-Induced Lung Cancer by Inducing Base Excision Repair.

Abdulkerim Eroglu,Emilio Balbuena,Junrui Cheng,Baxter Miller

doi:10.3390/antiox9070643

Abdulkerim Eroglu, Emilio Balbuena + Show 2 more

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https://doi.org/10.3390/antiox9070643

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Abstract

Background: Oxidative stress plays a critical role in lung cancer progression. Carotenoids are efficient antioxidants. The objective of this study was to explore the efficacy of all-trans retinoic acid (ATRA) and carotenoids in cigarette smoke-induced oxidative stress within A549 human lung cancer epithelial cells. Methods: A549 cells were pretreated with 1-nM, 10-nM, 100-nM, 1-μM and 10-μM ATRA, β-carotene (BC) and lycopene for 24 h, followed by exposure to cigarette smoke using a smoking chamber. Results: The OxyBlot analysis showed that smoking significantly increased oxidative stress, which was inhibited by lycopene at 1 nM and 10 nM (p < 0.05). In the cells exposed to smoke, lycopene increased 8-oxoguanine DNA glycosylase (OGG1) expression at 1 nM, 10 nM, 100 nM, and 1 μM (p < 0.05), but not at 10 μM. Lycopene at lower doses also improved Nei like DNA glycosylases (NEIL1, NEIL2, NEIL3), and connexin-43 (Cx43) protein levels (p < 0.05). Interestingly, lycopene at lower concentrations promoted OGG1 expression within the cells exposed to smoke to an even greater extent than the cells not exposed to smoke (p < 0.01). This may be attributed to the increased SR-B1 mRNA levels with cigarette smoke exposure (p < 0.05). Conclusions: Lycopene treatment at a lower dosage could inhibit smoke-induced oxidative stress and promote genome stability. These novel findings will shed light on the molecular mechanism of lycopene action against lung cancer.

Highlights

Lung cancer is the leading cause of cancer death, with eight million annual global deaths attributed to direct tobacco use, according to a report from World Health Organization (WHO) in 2019 [1]
By employing OxyBlot analysis, we found that the cells exposed to smoke presented a OxyBlot analysis, we found that the cells exposed smoke significantly significantly higher level of DNP-hydrazone in comparison to theto cells not presented exposed toa smoke, which higher level of DNP-hydrazone in comparison to the cells not exposed to smoke, which did notthe form did not form protein carbonization at all, indicating more oxidized protein formation within cells protein carbonization at all, indicating more oxidized protein formation the exposed cells exposed to exposed to smoke
There was our results showed that in the cells exposed to smoke, NEIL2 and NEIL3 protein concentrations were a trend of increasing 8-oxoguanine DNA glycosylase (OGG1) protein expression in the cells not exposed to smoke with lycopene significantly enhanced with lycopene treatment at 10 nM and 100 nM

Summary

Introduction

Lung cancer is the leading cause of cancer death, with eight million annual global deaths attributed to direct tobacco use, according to a report from World Health Organization (WHO) in 2019 [1]. Cigarette-smoking is one of the major environmental cues inducing the formation of reactive oxygen species (ROS) and the occurrence of oxidative stress, thereby resulting in damage to and modification of cellular macromolecules, and most importantly, genomic DNA that can lead to mutations [3]. To date, there are not yet effective treatments against smoke-induced oxidative stress or lung cancer. The objective of this study was to explore the efficacy of all-trans retinoic acid (ATRA) and carotenoids in cigarette smoke-induced oxidative stress within A549 human lung cancer epithelial cells. In the cells exposed to smoke, lycopene increased 8-oxoguanine DNA glycosylase (OGG1) expression at 1 nM, 10 nM, 100 nM, and 1 μM (p < 0.05), but not at 10 μM. Lycopene at lower doses improved Nei like DNA glycosylases (NEIL1, NEIL2, NEIL3), and connexin-43 (Cx43) protein levels (p < 0.05)

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