The Effect Of Irradiation With Curcumin As A Possible Form Of Amelanotic Melanoma Treatment.

Nowadays new medicines are being sought to effectively fight against melanoma. Metabolites of natural compounds have been used for antimelanoma therapy for a long time, but in recent years, new active substances of natural origin have been discovered with proven effects that interfere with the metabolism of tumor cells. The most interesting are compounds exhibiting low toxicity against normal cells, and selective cytotoxicity against cancer cells. One of these compounds is curcumin—a component of turmeric. Curcumin has immunomodulatory, anti-inflammatory, anticancer effects, affects the phase II enzymes and is a potent photosensitizer, thus showing strong potential for use in oncotherapy. Curcumin has been investigated as a potential photosensitizer (PS) in anticancer photodynamic therapy (PDT). The phototoxic effect of curcumin is dependent on proper formulations of the compound because of the lipophilic nature of the molecule and the extremely low water solubility at physiologic conditions. In the present study, the combination of curcumin was investigated in PDT using human melanoma amelanotic cell line (C32) and normal human fibroblasts from primary culture as control cells. The cells were maintained in culture and then treated with curcumin at concentrations of 5-50 μM for 2, 24 and 48. Then cells were irradiated with blue light (20 J/cm2) for 5 minutes and incubated for 24 hours. The efficacy of photodynamic effect was evaluated by viability assay (MTT). Additionally, cell death assay and cellular reactive oxygen species (ROS) assay were assessed. The intracellular distribution of curcumin after different time of incubation was visualized by CLSM method. The results suggest that curcumin may be a potent alternative to commonly used cytostatics. Depending on the curcumin concentration, the cell survival ranged from 18.95% of control cells after incubation with 50 μM curcumin to 0.91% after PDT. It has been shown that PDT with curcumin can increase oxidative stress and number of apoptotic and necrotic cells in comparison to incubation with curcumin without irradiation. The reduced and selective anticancer activity as compared to other drugs can be the basis for the use of curcumin also in complementary treatment of amelanotic melanoma. This study has revealed for the first time that PDT with curcumin appears to represent an efficient alternative for the treatment of amelanotic melanoma through the in situ application of the photosensitizer followed by irradiation of the photosensitizer-loaded area. Thus, the proposed protocol seems to be promising in the amelanotic melanoma, which is extremely resistant to standard chemo- and radiotherapy. Citation Format: Stanislaw Kwiatkowski, Dawid Przystupski, Krzysztof Kotowski, Agata Gorska, Weronika Bartosik, Aleksander Kielbik, Jolanta Saczko, Julita Kulbacka. The effect of irradiation with curcumin as a possible form of amelanotic melanoma treatment [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A08.