title: Depigmentation in melanomas increases the efficacy of hypericin-mediated photodynamic-induced cell death.
abstract: Melanoma is the main cause of death in skin cancers. Despite combating with early detection, resection and post-operative therapy, melanoma treatment remains unsuccessful and investigations into other forms of adjuvant therapy such as photodynamic therapy (PDT) are prudent. This study proposes that depigmentation i.e. the removal of the free radical scavenging pigment, melanin, in melanotic melanoma cells increases their susceptibility to PDT-induced cell death. Two human melanoma cell lines: one pigmented (Mel-1) and one amelanotic (A(375)) cell lines were used. Kojic acid (KA), a tyrosinase-specific inhibitor, was optimised to 6 μg/ml and shown to quantifiably inhibit melanin synthesis after a 3-day exposure. PDT on these cells resulted in a 3.82 fold increase of intracellular ROS production which correlated to 11% increase in cell death susceptibility compared to untreated controls. Moreover, cells allowed to regain their pigment failed to return to normal even after 72 h thus proving the effectiveness of PDT. Using a DPPH* assay, the results confirmed the scavenging properties of melanin (IC(50) 18.30 μg/ml) proving that this pigment may be one of the reasons for melanoma chemoresistance. Overall this study shows that pigment plays an important role in the efficacy of adjunctive PDT treatment and its removal enhances cell death susceptibility in melanomas.
authors.affiliation: Redox Laboratory, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925 Cape Town, South Africa.
authors.forename: Krishna V
authors.initials: KV
authors.lastname: Sharma
authors.forename: Lester M
authors.initials: LM
authors.lastname: Davids
mesh_terms: D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000473:pathology / Q000503:physiopathology*; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D010858:Pigmentation / Q000187:drug effects* / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
chemical_list: D000873:Anthracenes; D008543:Melanins; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin