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Updated: May 22, 2026
Quantification of Hypopigmentation Activity In Vitro
Published on: March 6, 2019
Depigmentation in melanomas increases the efficacy of hypericin-mediated photodynamic-induced cell death
Krishna V Sharma1, Lester M Davids
1Redox Laboratory, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925 Cape Town, South Africa.
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.
Insights
Removing melanin pigment from melanoma cells enhances their susceptibility to photodynamic therapy (PDT)-induced cell death. This suggests melanin contributes to chemoresistance, highlighting pigment
Area of Science:
- Oncology
- Dermatology
- Photochemistry
Background:
- Melanoma is a deadly skin cancer with challenging treatment outcomes.
- Adjuvant therapies like photodynamic therapy (PDT) are being explored for melanoma.
- Melanin, a pigment in melanoma cells, may influence treatment resistance.
Purpose of the Study:
- To investigate if depigmentation of melanoma cells increases their sensitivity to PDT.
- To determine the role of melanin in melanoma chemoresistance.
- To evaluate PDT efficacy in pigmented vs. amelanotic melanoma cells.
Main Methods:
- Utilized two human melanoma cell lines (pigmented and amelanotic).
- Inhibited melanin synthesis using Kojic acid (KA).
- Assessed cell death susceptibility and reactive oxygen species (ROS) production post-PDT.
- Quantified melanin's free radical scavenging properties using a DPPH assay.
Main Results:
- Kojic acid effectively inhibited melanin synthesis.
- PDT significantly increased ROS production and cell death in depigmented cells.
- Melanin demonstrated significant free radical scavenging properties (IC50 18.30 μg/ml).
- Depigmented cells showed a 3.82-fold increase in ROS and 11% higher cell death susceptibility.
Conclusions:
- Melanin pigment contributes to melanoma's resistance to PDT.
- Depigmentation enhances melanoma cell death susceptibility to PDT.
- Targeting melanin may improve the efficacy of adjuvant PDT in melanoma treatment.
