Inhibition of Survival Mechanisms and Cell Death Induction in Melanoma Following Photodynamic Therapy Mediated by Meso-5,10,15,20-tetrakis-(4-hydroxyphenyl)-porphyrin

Ioana Baldea; Sorina Danescu; Flaviu Tabaran; Adriana Gabriela Filip; Rodica Mariana Ion; Diana Elena Olteanu; Alexandra Cristina Sevastre-Berghian; Roxana Maria Decea; Cristian Iacovita; Daniela Hanganu; Mihai Cenariu

LAPSE

Living Archive for Process Systems Engineering

LAPSE:2023.28354

Published Article

LAPSE:2023.28354

Inhibition of Survival Mechanisms and Cell Death Induction in Melanoma Following Photodynamic Therapy Mediated by Meso-5,10,15,20-tetrakis-(4-hydroxyphenyl)-porphyrin

Ioana Baldea, Sorina Danescu, Flaviu Tabaran, Adriana Gabriela Filip, Rodica Mariana Ion, Diana Elena Olteanu, Alexandra Cristina Sevastre-Berghian, Roxana Maria Decea, Cristian Iacovita, Daniela Hanganu, Mihai Cenariu

April 11, 2023

(1) Background: Photodynamic therapy (PDT) involves the selective killing of tumor cells by the generation of reactive oxygen species using a photosensitizer (PS) activated by irradiation. In melanoma, PDT efficiency is altered by several mechanisms, such as the presence of melanin and melanosomes and pro-survival pathways mediated by transcription factors such as: AP-1 (activator protein), MITF (microphthalmia inducible transcription factor), HIF1α (hypoxia inducible factor), and NF-kB (nuclear factor kappa B). The study aimed to investigate the anti-melanoma effects of PDT mediated by meso-5,10,15,20-tetrakis-(4-hydroxyphenyl)-porphyrin (THPP) as a photosensitizer. (2) Methods: Cocultures of melanoma, two human, WM35 and M1−15, and murine B16-F10, with endothelial cells, were used. Cytotoxicity, oxidative damage, angiogenesis markers, and melanogenesis were assessed using colorimetry, flowcytometry, confocal microscopy, spectrophotometry, ELISA, and Western blotting. (3) Results: The maximal killing efficiency of PDT was reached in WM35, followed by M1−15, and then B16-F10, and it occurred through both apoptosis and necrosis. Although constitutive pigmentation diminished the PDT efficiency, de novo melanogenesis exhibited no protection. PDT increased TNFα, and inhibited NFkB, MITF, HIF1α, and AP1, leading to inflammation and angiogenesis markers’ inhibition. (4) Conclusions: THPP-mediated PDT efficiently induced cell death through apoptosis, necrosis, and the inhibition of pro-survival pathways mediated by NFkB, AP1, HIF1α, and MITF in the melanoma coculture models.

Record ID

LAPSE:2023.28354

Keywords

angiogenesis, inflammatory markers, melanoma–endothelial cells co-culture, mitochondrial apoptosis, oxidative stress damage, photodynamic therapy

Subject

Biosystems

Suggested Citation

Baldea I, Danescu S, Tabaran F, Filip AG, Ion RM, Olteanu DE, Sevastre-Berghian AC, Decea RM, Iacovita C, Hanganu D, Cenariu M. Inhibition of Survival Mechanisms and Cell Death Induction in Melanoma Following Photodynamic Therapy Mediated by Meso-5,10,15,20-tetrakis-(4-hydroxyphenyl)-porphyrin. (2023). LAPSE:2023.28354

Author Affiliations

Baldea I: Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor 1-3, 400012 Cluj-Napoca, Romania [ORCID]
Danescu S: Department of Dermatology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor 1-3, 400012 Cluj-Napoca, Romania
Tabaran F: Department of Morphopathology, University of Agricultural Studies and Veterinary Medicine, Calea Manastur 3-5, 400658 Cluj-Napoca, Romania [ORCID]
Filip AG: Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor 1-3, 400012 Cluj-Napoca, Romania [ORCID]
Ion RM: Nanomedicine Research Group, National Institute for Research & Development in Chemistry and Petrochemistry—ICECHIM, 202 Splaiul Independentei, 060024 Bucharest, Romania [ORCID]
Olteanu DE: Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor 1-3, 400012 Cluj-Napoca, Romania [ORCID]
Sevastre-Berghian AC: Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor 1-3, 400012 Cluj-Napoca, Romania
Decea RM: Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy, Clinicilor 1-3, 400012 Cluj-Napoca, Romania
Iacovita C: Department of Pharmaceutical Physics-Biophysics, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Pasteur St., 400349 Cluj-Napoca, Romania [ORCID]
Hanganu D: Department of Pharmacognosy, University of Medicine and Pharmacy Iuliu Hatieganu, 6 Pasteur St., 400349 Cluj-Napoca, Romania
Cenariu M: Department of Biochemistry, University of Agricultural Sciences and Veterinary Medicine, Calea Manastur 3-5, 400658 Cluj-Napoca, Romania

Journal Name

Processes

Volume

11

Issue

3

First Page

917

Year

2023

Publication Date

2023-03-17