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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Tryptophan and Its Selected Metabolites Modulate Melanoma-Cell Biology: A Preliminary In Vitro Study

  • Anna Michalak-Stoma1
  • Katarzyna Walczak2
  • Małgorzata Kowal2
  • Katarzyna Sawa-Wejksza3
  • Michał Chojnacki4
  • Marta Kinga Lemieszek4
  • Filip Stoma5
  • Dorota Krasowska1
5 affiliations
  1. 1Chair and Department of Dermatology, Venereology and Paediatric Dermatology, Medical University of Lublin, Staszica 11, 20-081 Lublin, Poland
  2. 2Laboratory for Immunology of Skin Diseases, Chair and Department of Dermatology, Venereology and Paediatric Dermatology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
  3. 3Department of Virology and Immunology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland
  4. 4Department of Medical Biology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland
  5. 5Chair and Department of Neurosurgery, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland
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Abstract

Tryptophan (TRP) and its metabolites are involved in numerous physiological and pathological processes within the skin. They may influence melanoma biology, but their role remains insufficiently understood. This study investigated the effects of TRP, anthranilic acid (AA), and cinnabarinic acid (CBA) in melanoma cells in vitro and their potential interaction with the B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor vemurafenib. A375, G361, and SK-MEL-3 melanoma cell lines and a THP-1-derived macrophage model were used. Cell proliferation and metabolic activity were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, migration using a scratch assay, and cell-cycle distribution by flow cytometry. Western blotting was used to analyze selected signaling proteins. Reactive oxygen species (ROS) and nitric oxide (NO) production were evaluated. Bioinformatic analyses investigated associations between BRAF and genes related to tryptophan metabolism and the kynurenine pathway. All compounds showed dose-dependent antiproliferative effects, with prolonged exposure increasing efficacy. TRP and AA increased G0/G1 cell-cycle arrest, whereas CBA increased the G2/M population. TRP also reduced A375 cell migration. All three compounds enhanced the antiproliferative effect of vemurafenib, with CBA showing the strongest effect (approximately 20%). Western blot analysis indicated modulation of p21 expression and ERK1/2 phosphorylation, suggesting implications for cell cycle and stress signaling pathways. Moreover, conditioned medium from A375 cells exposed to tested compounds affected cell viability, ROS, and NO production in THP-1-derived macrophages. TRP and its metabolites may be considered potential supportive agents for melanoma BRAF-targeted therapy. However, further in vivo studies are needed to clarify their therapeutic value and to elucidate the underlying molecular mechanisms.

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Cite

BibTeXRIS
BibTeX
@article{michalakstoma2026tryptophan,
  title = {{Tryptophan and Its Selected Metabolites Modulate Melanoma-Cell Biology: A Preliminary In Vitro Study}},
  author = {Anna Michalak-Stoma and Katarzyna Walczak and Małgorzata Kowal and Katarzyna Sawa-Wejksza and Michał Chojnacki and Marta Kinga Lemieszek and Filip Stoma and Dorota Krasowska},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = nov,
  doi = {10.3390/ijms27219908},
  url = {https://www.mdpi.com/1422-0067/27/21/9908},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Tryptophan and Its Selected Metabolites Modulate Melanoma-Cell Biology: A Preliminary In Vitro Study
AU  - Anna Michalak-Stoma
AU  - Katarzyna Walczak
AU  - Małgorzata Kowal
AU  - Katarzyna Sawa-Wejksza
AU  - Michał Chojnacki
AU  - Marta Kinga Lemieszek
AU  - Filip Stoma
AU  - Dorota Krasowska
PY  - 2026
DA  - 2026/11/05
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219908
UR  - https://www.mdpi.com/1422-0067/27/21/9908
AB  - Tryptophan (TRP) and its metabolites are involved in numerous physiological and pathological processes within the skin. They may influence melanoma biology, but their role remains insufficiently understood. This study investigated the effects of TRP, anthranilic acid (AA), and cinnabarinic acid (CBA) in melanoma cells in vitro and their potential interaction with the B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor vemurafenib. A375, G361, and SK-MEL-3 melanoma cell lines and a THP-1-derived macrophage model were used. Cell proliferation and metabolic activity were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, migration using a scratch assay, and cell-cycle distribution by flow cytometry. Western blotting was used to analyze selected signaling proteins. Reactive oxygen species (ROS) and nitric oxide (NO) production were evaluated. Bioinformatic analyses investigated associations between BRAF and genes related to tryptophan metabolism and the kynurenine pathway. All compounds showed dose-dependent antiproliferative effects, with prolonged exposure increasing efficacy. TRP and AA increased G0/G1 cell-cycle arrest, whereas CBA increased the G2/M population. TRP also reduced A375 cell migration. All three compounds enhanced the antiproliferative effect of vemurafenib, with CBA showing the strongest effect (approximately 20%). Western blot analysis indicated modulation of p21 expression and ERK1/2 phosphorylation, suggesting implications for cell cycle and stress signaling pathways. Moreover, conditioned medium from A375 cells exposed to tested compounds affected cell viability, ROS, and NO production in THP-1-derived macrophages. TRP and its metabolites may be considered potential supportive agents for melanoma BRAF-targeted therapy. However, further in vivo studies are needed to clarify their therapeutic value and to elucidate the underlying molecular mechanisms.
SN  - 1422-0067
ER  -