Abstract 769: Garcinol inhibits cancer stem cell-like phenotype via suppression of the Wnt/â-catenin /STAT3 axis signalling pathway in human non-small cell lung carcinomas

Abstract

Abstract Innate or acquired drug resistance and consequently, tumor relapse in lung cancer patients have been linked to the activities of cancer stem cells (CSCs). Therefore, targeting CSCs is suggested as an effective approach for non-small cell lung cancer (NSCLC) therapy. In this study, we demonstrated that Garcinol, a polyisoprenylated benzophenone isolated from the fruiting bodies of Garcinia indica, possessing anti-inflammatory, antioxidant, acetyltransferase inhibitory and anticancer activities, modulates the activities of lung cancer stem cells (LCSCs) and their associated aggressiveness. Here, we demonstrated the inhibitory effect of Garcinol on LCSC phenotype of human NSCLC cells by using the analytical drug cytotoxicity or cell viability, flow-cytometric and functional assay approach. Garcinol significantly diminished the ability of NSCLC cell lines, H441 and A549 to form spheres. In parallel assays, Garcinol inhibited differentiated lung cancer cell and LCSCs viability in a dose-dependent manner. Consistent with these observations, Flow cytometric data showed that Garcinol reduced putative LCSC pool, evidenced by the dose-dependent decreased proportion of side-population (SP) cells and associated ALDH activity in Garcinol-treated H441 cells, compared to the control group. Additionally, functional assays showed that Garcinol markedly diminished the ability of H441 and A549 cells to form colonies. Mechanistically, Garcinol impaired phosphorylation of LRP6, a co-receptor of Wnt and STAT3. In same assay, Garcinol downregulated â-catenin, Dvl2, Axin2, and Cyclin D1 expressions in NSCLC-generated spheres, suggesting its ability to regulate the Wnt/â-catenin signalling pathway. Put together, we demonstrated here that Garcinol modulates the LCSC phenotype via regulation of the Wnt/â-catenin signalling and inactivation of STAT3, thus, presenting Garcinol as a putative novel anti-LCSC therapeutic agent. Keywords - Garcinol, non-small cell lung cancer, cancer stem cells, Wnt/â-catenin signalling pathway, anti-cancer therapy, STAT3 Citation Format: Wen-Chien Huang. Garcinol inhibits cancer stem cell-like phenotype via suppression of the Wnt/â-catenin /STAT3 axis signalling pathway in human non-small cell lung carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 769.