Abstract 3378: Metformin protects head and neck cancer stem cells against DNA damage induced apoptosis

Abstract

Abstract The cancer stem cell hypothesis posits that within a tumor exists a distinct subpopulation of cells responsible for tumor initiation, progression, and maintenance. These cancer stem cells (CSCs) tend to be resistant to conventional chemotherapy and, like normal stem cells, possess the ability to self-renew and differentiate, thereby effecting tumor recurrence. Metformin, the most widely prescribed drug for the treatment of diabetes, has received attention in recent years as a potential anticancer agent capable of targeting cancer stem cells through such means as inhibiting cell proliferation and abrogating chemo-resistance. In the current study, we sought to determine the effects of Metformin on a putative head and neck squamous cell carcinoma (HNSCC) cancer stem cell culture. In contrast to the findings of previous studies, our data suggests that Metformin promotes properties of a cancer stem cell phenotype in HNSCC in vitro. Treatment with Metformin resulted in a dose-dependent induction of the stem cell genes CD44, BMI-1, Oct-4, and Nanog, as measured by qPCR. These results were supported by immunofluorescence data. Metformin treatment promoted self-renewal capacity of HNSCC stem cells, as demonstrated by the increase in size and number of tumorspheres formed in non-adherent and non-differentiating conditions. At various doses, treatment with Metformin alone had no effect on cell proliferation, as measured by MTS assay. Furthermore, when administered in combination with cisplatin, Metformin significantly protected against cisplatin-induced cell death, as demonstrated by MTS and TUNEL assays. Immunoblot experiments demonstrating a decrease in Akt phosphorylation upon treatment with Metformin suggests Metformin-mediated cytoprotection is independent of the Akt pathway. Other possible mechanisms are currently under investigation, including Metformin's ability to regulate autophagy. Although further in vivo studies are necessary, taken together, our findings suggest that Metformin may not be an effective therapeutic option for patients with HNSCC. 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 3378. doi:1538-7445.AM2012-3378