Caffeic Acid Phenethyl Ester Assisted by Reversible Electroporation—In Vitro Study on Human Melanoma Cells

Melanoma is one of the most serious skin cancers. The incidence of this malignant skin lesion is continuing to increase worldwide. Melanoma is resistant to chemotherapeutic drugs and highly metastatic. Surgical resection can only be used to treat melanoma in the early stages, while chemotherapy is limited due to melanoma multi-drug resistance. The overexpression of glutathione S-transferase (GST) may have a critical role in this resistance. Caffeic acid phenethyl ester (CAPE) is a natural phenolic compound, which occurs in many plants. Previous studies demonstrated that CAPE suppresses the growth of melanoma cells and induces reactive oxygen species generation. It is also known that bioactivation of CAPE to its corresponding quinone metabolite by tyrosinase would lead to GST inhibition and selective melanoma cell death. We investigated the biochemical toxicity of CAPE in combination with microsecond electropermeabilization in two human melanoma cell lines. Our results indicate that electroporation of melanoma cells in the presence of CAPE induced high oxidative stress, which correlates with high cytotoxicity. Moreover, it can disrupt the metabolism of cancer cells by inducing apoptotic cell death. Electroporation of melanoma cells may be an efficient CAPE delivery system, enabling the application of this compound, while reducing its dose and exposure time.