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

Autor: Klara Valyi-Nagy, Gnanasekar Munirathinam, Matthew A. Bork, Troy Skwor, Tibor Valyi-Nagy, Brandon Leviskas
Rok vydání: 2019
Předmět:
0301 basic medicine
Uveal Neoplasms
Necrosis
Light
medicine.medical_treatment
Photodynamic therapy
necrosis
lcsh:Chemistry
0302 clinical medicine
Photosensitizer
lcsh:QH301-705.5
Spectroscopy
bcl-2-Associated X Protein
chemistry.chemical_classification
reactive oxygen species
Photosensitizing Agents
Chemistry
apoptosis
General Medicine
Computer Science Applications
Gene Expression Regulation
Neoplastic
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
medicine.symptom
Programmed cell death
Cell Survival
Metalloporphyrins
Antineoplastic Agents
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Pd(T4)
Cell Line
Tumor
medicine
melanoma
Humans
Physical and Theoretical Chemistry
5-ALA
Molecular Biology
Reactive oxygen species
Organic Chemistry
Aminolevulinic Acid
blue light
Oncolytic virus
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Photochemotherapy
Apoptosis
Cancer cell
Cancer research
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 2, p 669 (2020)
Volume 21
Issue 2
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
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