Tetra-cationic platinum(II) porphyrins like a candidate photosensitizers to bind, selective and drug delivery for metastatic melanoma

• Published in: Journal of photochemistry and photobiology. B, Biology Vol. 202; p. 111725
• Main Authors: Couto, Gabriela Klein, Pacheco, Bruna Silveira, Borba, Victoria Mascarenhas, Junior, João Carlos Rodrigues, Oliveira, Thaís Larré, Segatto, Natália Vieira, Seixas, Fabiana Kommling, Acunha, Thiago V., Iglesias, Bernardo Almeida, Collares, Tiago
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01-01-2020; Elsevier BV
• Subjects: Actin; Animals; Annexin V; Anticancer properties; Antitumor activity; APO B-100, Cancer; Apoptosis; Apoptosis - drug effects; Bax protein; Binding Sites; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase-3; Caspase-9; Cations - chemistry; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell viability; CHO Cells; Confocal microscopy; Coupling (molecular); Cricetinae; Cricetulus; Cyclin-dependent kinase inhibitor p21; Cytoskeleton; Cytotoxicity; Drug Carriers - chemistry; Drug delivery; Drug delivery systems; Gene Expression Regulation - drug effects; GTP-binding protein; Humans; LDL receptor; Light; Low density lipoprotein; Melanoma; Melanoma - metabolism; Melanoma - pathology; Metastases; Metastasis; Molecular docking; Molecular Docking Simulation; p53 Protein; Photodynamic therapy; Photosensitivity; Photosensitizer; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Platinum; Platinum - chemistry; Platinum(II) porphyrins; Porphyrins; Porphyrins - chemistry; Protein folding; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Superoxide dismutase; Toxicity; Tumor cells; Platinum(II) porphyrins; APO B-100, Cancer; Photosensitizer; Molecular docking; LDL receptor
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2019.111725

Photodynamic therapy (PDT) is an expanding treatment modality due to its minimally invasive localized activity and few adverse effects. This therapy requires photosensitive compounds, which have high sensitivity to light exposure. Thus, in this work, the in vitro antitumor activity of meso-tetra(3- and 4-pyridyl)porphyrins (3-TPyP and 4-TPyP) in metastatic melanoma cell (WM1366 line) and non-tumoral Ovarian lineage Chinese Hamister (CHO) was evaluated using photodynamic process. Cell viability tests, molecular docking, annexin V, confocal microscopy and qRT-PCR were performed. Our results show that both porphyrins inhibited the viability of metastatic melanoma cells when exposed to light and did not alter viability in the dark. In addition, they did not demonstrate cytotoxicity in non-tumor cells. Molecular coupling demonstrated platinum porphyrin affinity for the N-terminal region of APO B-100, LDL receptor, and therefore of the cells under study. Genes such as Caspase 3 and 9, P21, Bax / BCL2, MnSod and GSH showed increased expression. For meta isomer 3-PtTPyP treatment, caspase-9 and caspase-3 expression levels showed a 4.89 and 3.23-fold increase, respectively, while for the para isomer 4-PtTPyP, this change was 3.77 and 12.16-fold, respectively. We also observed an upregulated expression of p21, a protein well-known by its action in cell cycle arrest in a p53-dependent manner. Conclusion: 3-PtTPyP and 4-PtTPyP demonstrated antitumor effect on WM1366 cells, inducing apoptosis and significant alteration of cell cytoskeleton actin. Our work shows that platinum(II) porphyrins may be promising photosensitizers for the treatment of metastatic melanoma by PDT.
•Platinum(II) porphyrins are good candidates for photosensitizer.•Platinum(II) porphyrins alter cellular actin organization.•Platinum(II) porphyrins increased the number of total apoptotic cells.•Caspases 3 and 9 are involved in the mechanism of death of platinum porphyrins.•Platinum(II) porphyrins have affinity for LDL receptor.