Honokiol inhibits lung tumorigenesis through inhibition of mitochondrial function. Cancer Prev Res (Phila) 2014 Nov;7(11):1149-59
Date
09/24/2014Pubmed ID
25245764Pubmed Central ID
PMC6010030DOI
10.1158/1940-6207.CAPR-14-0091Scopus ID
2-s2.0-84910118566 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
Honokiol is an important bioactive compound found in the bark of Magnolia tree. It is a nonadipogenic PPARĪ³ 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 lung squamous cell carcinoma (SCC). This model system uses the carcinogen N-nitroso-trischloroethylurea (NTCU), which is applied topically, reliably triggering the development of SCC within 24 to 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 changed redox status 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.
Author List
Pan J, Zhang Q, Liu Q, Komas SM, Kalyanaraman B, Lubet RA, Wang Y, You MAuthor
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnimals
Anticarcinogenic Agents
Apoptosis
Biphenyl Compounds
Bronchi
Carcinogens
Carcinoma, Squamous Cell
Carmustine
Caspase 3
Caspase 7
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Green Fluorescent Proteins
Humans
Lignans
Lung Neoplasms
Mice
Mitochondria
Neoplasm Transplantation
Oxidation-Reduction
Reactive Oxygen Species