How does pheomelanin synthesis contribute to melanomagenesis?: Two distinct mechanisms could explain the carcinogenicity of pheomelanin synthesis
Open accessAbstract
Recently, we reported that melanoma risk in redheads is linked not only to pale skin, but also to the synthesis of the pigment – called pheomelanin – that gives red hair its color. We demonstrated that pheomelanin synthesis is associated with increased oxidative stress in the skin, yet we have not uncovered the chemical pathway between the molecule pheomelanin and the DNA damage that drives melanoma formation. Here, we hypothesize two possible pathways. On one hand, pheomelanin might generate reactive oxygen species (ROS) that directly or indirectly cause oxidative DNA damage. On the other hand, pheomelanin synthesis might consume cellular antioxidant stores and make the cell nucleus more vulnerable to other endogenous ROS. Uncovering the mechanistic pathway between pheomelanin and oxidative DNA damage will be an important step in developing strategies to lower melanoma risk in redheads.
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Pheomelanin can deplete cysteine-based antioxidants, such as GSH, thereby contributing further to the vulnerability of melanocytes to oxidative damage and melanomagenesis.
“In addition, pheomelanin can deplete cysteine-based antioxidants, such as GSH, thereby contributing further to the vulnerability of melanocytes to oxidative damage and melanomagenesis [ 62 ].”
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- Authors
- Morgan, A. M., Lo, J., & Fisher, D. E.
- Affiliations
- Massachusetts General Hospital (US)
- Corresponding author
- Morgan, Ann M.
- Venue
- BioEssays
- Publisher
- Wiley
- Published
- 2013-05-07
- Volume
- 35
- Issue
- 8
- Pages
- 672-676
- ISSN
- 0265-9247 (ISSN-L)
- 1521-1878
- PMC
- PMC4033715
- OpenAlex
- W1946161494
- Cited by
- 104
- References
- 26
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 13 · 2023: 14 · 2022: 8 · 2021: 4 · 2020: 9 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 1
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- BioEssays (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM007753)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR043369)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- melanomagenesis, melanoma risk, redheads, oxidative DNA damage, reactive oxygen species, oxidative stress, antioxidant depletion, skin pigmentation, melanoma prevention
- MeSH terms
- Animals, Antioxidants, Cell Nucleus, DNA Damage, Glutathione, Humans, Melanins, Melanocytes, Melanoma, Pigmentation, Risk Factors, Skin, Ultraviolet Rays, Gene Expression Regulation, Neoplastic, Reactive Oxygen Species, Oxidative Stress, Mice
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