Molecular insights: Suppression of EGFR and AKT activation by a small molecule in non-small cell lung cancer
Balaji Chandrasekaran1,*, Ashish Tyagi1,*, Arun K. Sharma2, Lu Cai3, Murali Ankem1 and Chendil Damodaran1
1 Department of Urology, University of Louisville, Louisville, KY, USA
2 Department of Pharmacology, Penn State University, Hershey, PA, USA
3 Pediatrics Research Institute, The Department of Pediatrics of the University of Louisville, Louisville, USA
* Both authors contributed equally
Correspondence:
Chendil Damodaran, email:
Keywords: growth inhibition, EGFR, AKT, lung cancer
Received: August 24, 2017 Accepted: October 17, 2017 Published: October 24, 2017
Abstract
Epidermal growth factor receptor (EGFR) activation events and the mammalian target of rampamycin (mTOR) are considered important therapeutic targets in alleviating cancer conditions. The current treatment paradigm has shifted to personalized treatment strategies with tyrosine kinase inhibitors (TKIs) or anaplastic lymphoma kinase (ALK) inhibitors, due to low survival rates in non-small cell lung cancer (NSCLC) in terms of the prevailing platinum-based therapy. In the present study, we examined the anticancer potential of Verrucarin J (VJ), a small molecule, in NSCLC cell lines (H460 and A549). The small molecule significantly inhibited cell growth, proliferation, colony forming ability, and induced apoptosis in both lung cancer cell lines. The inhibitory effects on EGFR (pEGFR –tyr1173) and AKT (pAKT Serine473) signaling, downregulates downstream pro-survival signaling (mTOR and NF-κB) in cancer cell lines. In addition, VJ abrogated invasive and migratory potential of A549 and H460 cells. We also observed a downregulation of mesenchymal markers such as N-cadherin, Slug, β-catenin, and vimentin expression in both cell lines. Our results suggest that VJ inhibited cancer cell growth and could be a potent molecule to inhibit EGFR and AKT signaling in NSCLC.
