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J Med Chem ; 63(3): 1328-1336, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-31940202

RESUMO

Malignant melanoma is an aggressive skin cancer with poor survival outcomes for patients diagnosed at an advanced stage. While targeted serine/threonine-protein kinase B-Raf (BRAF) and immune checkpoint inhibitors have improved survival outcomes for a proportion of these patients, response rates remain variable. There is a need, therefore, for more effective treatments to bolster the options available for melanoma patients. In this manuscript, we covalently attached Rose Bengal (RB) to the amphipathic peptide (AMP) C(KLAKLAK)2 and determined the effectiveness of the resulting RB-C(KLAKLAK)2 conjugate as a photodynamic therapy (PDT) sensitizer. RB-C(KLAKLAK)2-mediated PDT treatment of subcutaneous B16-F10-Luc2 tumors in C57 mice resulted in lesions that were 479% smaller at the end of the study than animals treated with RB-mediated PDT. The synergistic effect between RB and C(KLAKLAK)2 has been attributed to the AMP sensitizing cells to reactive oxygen species (ROS), making them more susceptible to ROS-induced oxidative stress.


Assuntos
Antineoplásicos/uso terapêutico , Melanoma/tratamento farmacológico , Peptídeos/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Rosa Bengala/análogos & derivados , Rosa Bengala/uso terapêutico , Sequência de Aminoácidos , Animais , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Camundongos SCID , Necrose/induzido quimicamente , Peptídeos/síntese química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Espécies Reativas de Oxigênio/metabolismo
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