Abstract 2001: Caffeic acid phenethyl ester inhibits growth of human lung adenocarcinoma cells with an epidermal growth factor receptor T790M mutation susceptible property

Abstract

Abstract Purpose: Target therapeutics targeting epidermal growth factor receptor (EGFR) effectively kills non-small cell lung cancer cells along with a high proportion acquires T790M mutation of EGFR, an amino acid alteration likely causing drug resistance. Caffeic acid phenethyl ester (CAPE), a naturally occurring small molecule isolated from honeybee propolis, is known to possess preferential bioactivity against lung cancer cells. Materials and Methods: In this study, we evaluated the effect of CAPE on A549 (EGFR wild-type) and H1975 (EGFR T790M mutation) human lung adenocarcinoma cells by using assays as follows: MTS for viability, DNA histogram for hypoploidy and cell cycle analysis, DiOC6(3) staining for mitochondrial transmembrane potential, and Western blotting for caspase-3 cleavage Results: We found that CAPE inhibited the growth of lung adenocarcinoma H1975 cells with an extent greater than A549 (IC50 approximate 5 versus 10 mg/mL) after 24 - 48 h treatment. This differential growth inhibition was accompanied by much higher percentages of sub-G1 (7.5 folds) and G2/M arrest (2.6 folds) in H1975 cells. No significant difference could be seen for changes in mitochondrial transmembrane potential and caspase-3 cleavage, indicating a mitochondria-independent and caspase-3-inependent pathway involved. Conclusion: It suggests that CAPE may have potential to be developed as a small-molecule therapeutics against lung adenocarcinoma cells harboring wild-type epidermal growth factor receptor and, more effectively, the T790M-mutated clone. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2001. doi:1538-7445.AM2012-2001