Honokiol suppresses lung tumorigenesis by targeting EGFR and its downstream effectors.

摘要: // Jung Min Song 1 , Arunkumar Anandharaj Pramod Upadhyaya Ameya R. Kirtane 2 Jong-Hyuk Kim 1, 4 Kwon Ho Hong 3 Jayanth Panyam Fekadu Kassie Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA Department Pharmaceutics, Institute for Therapeutics Discovery and Development, 55414, Veterinary Clinical Sciences, College Medicine, Saint Paul, 55108, Correspondence to: Kassie, email: kassi012@umn.edu Keywords: chemoprevention, honokiol, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, lung tumor, EGFR Received: April 26, 2016      Accepted: July 10, Published: 21, 2016 ABSTRACT Since epidermal growth factor receptor (EGFR) is commonly deregulated in pre-malignant epithelium, targeting may arrest the development cancer. Here, we showed that honokiol (2.5–7.5 μM), a bioactive compound Magnolia officinalis differentially suppressed proliferation (up to 93%) induced apoptosis 61%) overexpressing tumorigenic bronchial cells these effects were paralleled by downregulation phospho-EGFR, phospho-Akt, phospho-STAT3 cell cycle-related proteins as early 6–12 h post-treatment. Autocrine secretion EGF sensitized 1170 honokiol. Molecular docking studies indicated binds tyrosine kinase domain although it was less efficient than erlotinib. However, anti-proliferative pro-apoptotic activities stronger those Upon combinatory treatment, erlotinib resistant H1650 H1975 Furthermore, mouse tumor bioassay, intranasal instillation liposomal (5 mg/kg) 14 weeks reduced size multiplicity (49%) tumors level total- phospho-Akt phospho-STAT3. Overall, our results indicate promising candidate suppress even progression driven deregulation.