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

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.