Abstract 5551: Anti-tumorigenic function of polyphenolic compounds on gefitinib resistant lung cancer

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA EGFR-mutant non-small cell lung cancer (NSCLC) is initially very sensitive to EGFR tyrosine kinase inhibitors (TKIs). Even with the remarkable effect of EGFR TKIs, patients eventually acquire resistance to gefitinib or elortinib, leading to a clinical challenge for overcoming TKI resistance. Some polyphenolic compounds are known as potential anti-tumorigenic compounds, such as resveratrol, curcumin or EGCG. However the function of these natural compounds in resistant NSCLC remains to be elucidated. Here, we identified a polyphenolic compound (named as compound A) from screening a set of natural compounds for anti-cancer effects on NSCLC. We found that compound A is a potential anticancer agent both in vivo and in vitro. Moreover, the growth inhibition of compound A turns out to be selective for cancer cells. Next, we further evaluated the growth inhibitory effect of compound A in two sets of NSCLC panels which are either sensitive or resistant to gefitinib treatment. Interestingly, the cell lines which are resistant to gefitinib are highly sensitive to compound A treatment, whereas the gefitinib-sensitive (GS) cell lines are not responsive to the compound A treatment. In gefitinib resistant (GR) cells, compound A increases expression of autophagy markers, p62 and LC3, which might result in the growth inhibition of the GR panel of cells but not in the GS cell panel. Moreover, we profiled the metabolic genes in the GR and GS cell lines. Surprisingly, compound A treatment significantly reduces the expression of a subset of enzymes associated with Warburg effect, which includes GLUT1, LDHA, PDK1, HK1, and HK2. As a result, compound A decreases Warburg effect, subsequently suppressing cell proliferation, especially of the GR cell lines. Taken together, compound A decreases Warburg effect and up-regulates autophagy process that may contribute to tumor suppression function of compound A in gefitinib-resistant cancer. Citation Format: Ai N. H. Phan, Yangsik Jeong. Anti-tumorigenic function of polyphenolic compounds on gefitinib resistant lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5551. doi:10.1158/1538-7445.AM2015-5551