Abstract 824: A novel mechanism of areca nut-induced oral cancer is through the conversion of cancer stem cells to acquire malignant phenotypes

Abstract

Abstract Areca nut is one of the most commonly used psychoactive substance worldwide. It is has been identified as a primary carcinogen of oral cancer in Southeast Asia. Previous studies to examine the effects of this carcinogen often used short-term and high-dose treatment of area nut extract (ANE) as a research model. To elucidate the molecular effects of areca nut and mimic patient chronic exposure situation, we established four areca nut extract (ANE)-trained oral cancer sublines by treating cells with low-dose of ANE (IC30, dose for 30% growth inhibition) for 2 months. Without evidence of cellular senescence, these sublines exhibited significant increases in invasive ability, along with the up-regulation of MMP1 and the reversed expression of epithelial-mesenchymal transition markers. These sublines also showed more resistant to chemotherapeutics and irradiation, which was associated with the over-expression of ABCG2 transporters, increased production of anti-oxidative enzymes, and insensitive to ROS induction. Furthermore, these chronically treated cells possessed characteristics of cancer stem cells, as indicated by enrichment of CD24-/CD44+ population, enhancing spheroid cell formation, and increasing expressions of stemness associated molecules, including Slug, Twist1, Sox9, and Grp78. Thus, we concluded that chronic areca nut exposure induces a pleotropic effect on stemness regulators that facilitates the conversion of cancer stem cells to acquire malignant transformation in oral cancer. This novel finding provides valuable knowledge on areca nut-induced oral carcinogenesis. Citation Format: Yi-Chen Li, Ann-Joy Cheng. A novel mechanism of areca nut-induced oral cancer is through the conversion of cancer stem cells to acquire malignant phenotypes. [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 824. doi:10.1158/1538-7445.AM2015-824