Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function

Menée in vitro et à l'aide d'un modèle de carcinome épidermoïde du poumon, cette étude met en évidence un mécanisme par lequel l'honokiol, un composé présent dans l'écorce de Magnolia, inhibe la tumorigenèse en agissant sur la respiration mitochondriale des cellules tumorales

Résumé en anglais

Honokiol is an important bioactive compound found in the bark of Magnolia tree. It is a non-adipogenic PPARγ agonist, and capable of inhibiting the growth of a variety of tumor types both in vitro and in xenograft models. However, to fully appreciate the potential chemopreventive activity of honokiol, a less artificial model system is required. To that end, this study examined the chemopreventive efficacy of honokiol in an initiation model of squamous cell lung cancer (SCC). This model system uses the carcinogen N-nitroso-trischloroethylurea (NTCU) which is applied topically, reliably triggering the development of SCC within 24-26 weeks. Administration of honokiol significantly reduced the percentage of bronchial that exhibit abnormal lung SCC histology from 24.4% bronchial in control to 11.0% bronchial in honokiol treated group (p= 0.01) while protecting normal bronchial histology (present in 20.5% of bronchial in control group and 38.5% of bronchial in honokiol treated group (p= 0.004)). P63 staining at the SCC site confirmed the lung SCCs phenotype. In vitro studies revealed that honokiol inhibited lung SCC cells proliferation, arrested cells at the G1/S cell cycle checkpoint, while also leading to increased apoptosis. Our study showed that interfering with mitochondrial respiration is a novel mechanism by which honokiol increased generation of reactive oxygen species (ROS) in the mitochondria, triggered apoptosis, and finally leads to the inhibition of lung SCC. This novel mechanism of targeting mitochondrial suggests honokiol as a potential lung SCC chemopreventive agent.