Targeting chemical carcinogenesis: α-pinene and D-limonene as chemopreventive agents against NNK/ TCDD- and urethane-induced lung tumorigenesis

Kuo-Ching Huang^a,b,1, Vui-Hyen Chew^a,1, Yu-Ying Chen^a,1, Huey-Jen Su^a, Hao-Ting Chang^c, Rong-Jane Chen^d,*, Ying-Jan Wang^a,**

^aDepartment of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70428, Taiwan

^bDivision of Nephrology, Department of Internal Medicine, Chi Mei Hospital, Liouying, No.201, Liuying Dist., Tainan City 73657, Taiwan

^cDepartment of Geomatics, College of Engineering, National Cheng Kung University, Tainan, Taiwan

^dDepartment of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan

Lung cancer is the leading cause of cancer-related deaths worldwide, driven by carcinogens such as tobacco-derived nitrosamines, dioxins, and urethane. This study evaluated the chemopreventive effects of two monoterpenes, α-pinene and D-limonene, using NNK/TCDD- and urethane-induced lung tumor models and A549 lung cancer cells. Both compounds significantly reduce tumor number and size, with enhanced effects when combined. Mechanistic studies revealed suppression of PRC1, β-catenin, and c-Myc, alongside activation of p53, Bax, and caspase-3, indicating inhibition of the PRC1—Wnt/β-catenin pathway and induction of apoptosis. These findings suggest α-pinene and D-limonene as safe, promising agents for lung cancer chemoprevention.