Metalloporphyrin Pd(T4) Exhibits Oncolytic Activity and Cumulative Effects with 5-ALA Photodynamic Treatment against C918 Cells

International Journal of Molecular Sciences

Gnanasekar Munirathinam¹  Brandon Leviskas²  Matthew Bork²  Troy Skwor²  Tibor Valyi-Nagy³  Klara Valyi-Nagy³ 

[1] Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61108, USA;Department of Chemical and Biological Sciences, Rockford University, Rockford, IL 61107, USA;Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA;

关键词: pd(t4);    melanoma;    reactive oxygen species;    5-ala;    blue light;    apoptosis;    necrosis;   

DOI  :  10.3390/ijms21020669

来源: DOAJ

【 摘 要 】

Photodynamic therapy is a non-invasive method where light activates a photosensitizer bound to cancer cells, generating reactive oxygen species and resulting in cell death. This study assessed the oncolytic potential of photodynamic therapy, comparing European Medicines Agency and United States Food and Drug Administration-approved 5-aminolevulinic acid (5-ALA) to a metalloporphyrin, Pd(T4), against a highly invasive uveal melanoma cell line (C918) in two- and three-dimensional models in vitro. Epithelial monolayer studies displayed strong oncolytic effects (>70%) when utilizing Pd(T4) at a fraction of the concentration, and reduced pre-illumination time compared to 5-ALA post-405 nm irradiance. When analyzed at sub-optimal concentrations, application of Pd(T4) and 5-ALA with 405 nm displayed cumulative effects. Lethality from Pd(T4)-photodynamic therapy was maintained within a three-dimensional model, including the more resilient vasculogenic mimicry-forming cells, though at lower rates. At high concentrations, modality of cell death exhibited necrosis partially dependent on reactive oxygen species. However, sub-optimal concentrations of photosensitizer exhibited an apoptotic protein expression profile characterized by increased Bax/Bcl-2 ratio and endoplasmic stress-related proteins, along with downregulation of apoptotic inhibitors CIAP-1 and -2. Together, our results indicate Pd(T4) as a strong photosensitizer alone and in combination with 5-ALA against C918 cells.

【 授权许可】

Unknown