The Association of Propranolol with 2-Deoxy-D-Glucose Reduces the Metabolism and the Proliferation of Cutaneous Squamous Carcinoma A431 Cell Line

Abstract

Non-selective β-blocking (±)-Propranolol Hydrochloride was demonstrated to improve the progression-free survival of oncological patients. Since the expression of β-adrenoceptors in the epidermal squamous cell carcinoma was described, we hypothesized that the topical application of a β- adrenoceptors-blockers over the tumor lesion may decrease its extension before the surgical excision, becoming an adjuvant therapy against cutaneous squamous cell carcinoma. However, it is known that β-AR-blocker anti-cancer activity as a single agent is limited. Hence, we suggested that the combination of propranolol with the glucose analog 2-Deoxy-D-glucose could improve its antiproliferative effect through the induction of metabolic stress. Propranolol and 2-Deoxy-D-glucose effect on A431 squamous cell carcinoma and normal keratinocytes evaluating metabolic activity, proliferation and apoptosis through MTT, immunofluorescence Ki-67 and AnnexinV assays, cell cycle analysis and migration assay. Our results demonstrated that the addition of 2-Deoxy-D-glucose low dose to propranolol improve its effect on reduction of A431 cells metabolism and proliferation, similar effect was observed on HaCaT viability and mobility. However, the HaCaT migration ability is not completely compromised. The combination of propranolol with a low dose of 2-Deoxy-D-glucose could be a promising treatment to be topically applied avoiding systemic adverse effects in patients with cutaneous squamous cell carcinoma.