ArticleJournal of the National Cancer Institute2009
Influence of melanosome dynamics on melanoma drug sensitivity.
Article in Journal of the National Cancer Institute, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 89 citations in OpenAlex.
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- Photodynamic Therapy Directed to Melanoma Skin Cancer by Thermosensitive Hydrogel Containing Chlorophyll A.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells.International journal of molecular sciences · 2023Article
- Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light ApplicationNanomaterials (Basel, Switzerland) · 2023Article
- Structural analysis of melanosomes in living mammalian cells using scanning electron-assisted dielectric microscopy with deep neural network.Computational and structural biotechnology journal · 2023Article
- Review
- Melanoma Detection by AFM Indentation of Histological Specimens.Diagnostics (Basel, Switzerland) · 2022Article
- Combined Therapy with Dacarbazine and Hyperthermia Induces Cytotoxicity in A375 and MNT-1 Melanoma Cells.International journal of molecular sciences · 2022Article
- New panel of biomarkers to discriminate between amelanotic and melanotic metastatic melanoma.Frontiers in oncology · 2022Article
- Heterogeneity of tyrosine-based melanin anabolism regulates pulmonary and cerebral organotropic colonization microenvironment of melanoma cells.Theranostics · 2022Article
- Melanization as unfavorable factor in amelanotic melanoma cell biology.Protoplasma · 2021Article
- Synergistic melanoma cell death mediated by inhibition of both MCL1 and BCL2 in high-risk tumors driven by NF1/PTEN loss.Oncogene · 2021Article
- Evaluation of Polymeric Matrix Loaded with Melatonin for Wound Dressing.International journal of molecular sciences · 2021Article
- Targeting SIRT2 Sensitizes Melanoma Cells to Cisplatin via an EGFR-Dependent Mechanism.International journal of molecular sciences · 2021Article
- Classification of node-positive melanomas into prognostic subgroups using keratin, immune, and melanogenesis expression patterns.Oncogene · 2021Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMalignant melanomas are intrinsically resistant to many conventional treatments, such as radiation and chemotherapy, for reasons that are poorly understood. Here we propose and test a model that explains drug resistance or sensitivity in terms of melanosome dynamics.
methodsThe growth and sensitivity to cisplatin of MNT-1 cells, which are melanotic and enriched with mature stage III and IV melanosomes, and SK-MEL-28 cells, which have only immature stage I and II melanosomes, were compared using clonogenic assays. Differences in pigmentation, melanosome stages, melanosome number, and cellular structures in different cell lines in response to various treatments were examined by electron microscopy. The relative numbers of melanosomes of different stages were compared after treatment with 1-phenyl-2-thiourea. The relationship between drug transporter function and endogenous melanogenic toxicity was assessed by treating cells with the cyclosporin analog PSC-833 and by assessing vacuole formation and cell growth inhibition. All statistical tests were two-sided.
resultsEndogenous melanogenic cytotoxicity, produced by damaged melanosomes, resulted in pronounced cell growth inhibition in MNT-1 cells compared with amelanotic SK-MEL-28 cells. The sensitivity to CDDP of MNT-1 cells was 3.8-fold higher than that of SK-MEL-28 cells (mean IC(50) for SK-MEL-28 and MNT-1 = 2.13 microM and 0.56 microM, respectively; difference = 1.57 microM, 95% confidence interval = 1.45 to 1.69; P = .0017). After treatment with 6.7 microM CDDP for 72 hours, the number of stage II-III melanosomes in surviving MNT-1 cells was 6.8-fold that of untreated cells. Modulation of MNT-1 cells to earlier-stage (II, II-III, III) melanosomes by treatment with the tyrosinase inhibitor 1-phenyl-2-thiourea dramatically increased CDDP resistance. Furthermore, PSC-833 principally suppressed MNT-1 melanotic cell growth via an elevation of autophagosome-like vacuolar structures, possibly by inhibiting melanosome membrane transporters.
conclusionsMelanosome dynamics (including their biogenesis, density, status, and structural integrity) regulate the drug resistance of melanoma cells. Manipulation of melanosome functions may be an effective way to enhance the therapeutic activity of anticancer drugs against melanoma.
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