Mechanisms of curcumin-based photodynamic therapy and its effects in combination with electroporation: An in vitro and molecular dynamics study

Abstract

Photodynamic therapy (PDT) and electrochemotherapy (ECT) are two methods designed to enhance the anticancer potential of various drugs. Various clinical trials proved the efficacy of both ECT and PDT in melanoma treatment. Curcumin is a natural polyphenolic compound with high anticancer potential against melanoma due to its light absorption properties and toxicity towards cancer cells; however, high reactivity and amphipathic structure of curcumin are limiting its utility. This study aimed to propose the most effective protocol for antimelanoma combination of both therapies (PDT and ECT) in the context of curcumin. The in vitro studies were carried on melanotic melanoma (A375), amelanotic melanoma (C32) and fibroblast (HGF) cell lines. In molecular dynamics studies curcumin presented the single-layer localization in the water-membrane interphase. Further, the mass spectrometry studies exposed that during the PDT treatment curcumin is degraded to vanillin, feruloylmethane, and ferulic acid. Instant ECT with curcumin followed by PDT is the most efficient approach due to its selective genotoxicity towards malignant cells. The metabolic activity of fibroblasts decreased, however, at the same time the fragmentation of DNA did not occur. Additionally, instant PDT with curcumin followed by ECT after 3 h of incubation was a therapy selective towards melanotic melanoma.

Keywords: Curcumin; Curcumin degradation; Curcumin localization; Electrochemotherapy; Melanoma; Photodynamic therapy.