The Association of Propranolol with 2DG Reduces the Metabolism and the Proliferation of Cutaneous Squamous Cell Carcinoma A431 Cell Line

Abstract

The non-selective β-blocking (±)-Propranolol Hydrochloride was demonstrated to improve the progression-free survival of patients and to reduce the incidence of different cancer types. Since the expression of β-adrenoceptors (β-AR) in the A431 squamous cell carcinoma (cSCC) human cells was described, we had suggested that cSCC proliferation may be controlled by using β-AR-blockers. Thus, we hypothesized that the topical application of a β-AR-blocker over the tumor lesion may decrease/restrain its extension before the surgical excision becoming an adjuvant\therapy against cSCC. 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 (2-DG) could improve its antiproliferative effect through the induction of metabolic stress. Our results have demonstrated that the addition of 2DG to (±)-Propranolol Hydrochloride therapy can improve its effect on A431 cells metabolism and proliferation, suggesting that the combination of (±)-Propranolol Hydrochloride with low dose of 2DG could be a promising treatment to be topically applied as an adjuvant pre-surgical therapy against cSCC, aiming to decrease the size of the injury before the surgical procedure, avoiding systemic adverse effects to the patient.