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.

Lycopene, a naturally occurring non-provitamin A carotenoid pigment, is responsible for the red to pink colors in tomato, watermelon, red bell peppers, and pink guava. There are many health benefits attributed to lycopene including but not limited to its antioxidant activity. According to the American Lung Association’s State of Lung Cancer, lung cancer is still the leading cause of cancer death in the United States. Other chronic lung diseases such as asthma, emphysema, and chronic obstructive pulmonary disease are high prevalence. This chapter summarizes lycopene’s protective role against lung diseases in both in vitro and in vivo studies. While it has been demonstrated that circulating lycopene can be used as a biomarker for several lung diseases, further studies are warranted to establish that. We aim to provide insights into how lycopene can remedy for lung diseases, including lung cancer.