Combination of Cl-IB-MECA with paclitaxel is a highly effective cytotoxic therapy causing mTOR-dependent autophagy and mitotic catastrophe on human melanoma cells

Purpose Metastatic melanoma is the deadliest form of skin cancer. It is highly resistant to conventional therapies, particularly to drugs that cause apoptosis as the main anticancer mechanism. Recently, induction of autophagic cell death is emerging as a novel therapeutic target for apoptotic-resistant cancers. We aimed to investigate the underlying mechanisms elicited by the cytotoxic combination of 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5′-N-methyl-uronamide (Cl-IB-MECA, a selective A3 adenosine receptor agonist; 10 μM) and paclitaxel (10 ng/mL) on human C32 and A375 melanoma cell lines.