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J Med Chem ; 63(3): 1328-1336, 2020 02 13.
Article in English | MEDLINE | ID: mdl-31940202

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Melanoma/drug therapy , Peptides/therapeutic use , Photosensitizing Agents/therapeutic use , Rose Bengal/analogs & derivatives , Rose Bengal/therapeutic use , Amino Acid Sequence , Animals , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Line, Tumor , Humans , Mice, SCID , Necrosis/chemically induced , Peptides/chemical synthesis , Photochemotherapy/methods , Photosensitizing Agents/chemical synthesis , Reactive Oxygen Species/metabolism
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