Cell-type dependent response of melanoma cells to aloe emodin

► Mechanism as well as the outcome of AE action against melanoma is defined by cell specificity. ► Induction of differentiation vs. apoptotic cell death is oppositely regulated by most important signals, ERK1/2 and Akt. ► Apoptotic cell death is triggered even in cells with permanently activated Akt. ► Independently from different intracellular response AE antagonized chemotherapy.