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Melatonin and Vitamins: New Insights into Cancer Therapies
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Melatonin and Vitamins: New Insights into Cancer Therapies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 29 August 2024 | Viewed by 2227

Special Issue Editor

Dr. Konrad Kleszczyński

E-Mail Website
Guest Editor
Department of Dermatology, University of Münster, 48149 Münster, Germany
Interests: dermato-endocrinology; melanoma; melanogenesis; human skin; photobiology; cutaneous cells; mitochondria; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recently, numerous studies have provided new insights into the new biological capacities and health-related or clinical applications of melatonin and vitamins, particularly vitamin D, as well as its homologues. These substances have been widely documented as differentiative ones with beneficial impacts, such as the biological regulation of endogenous synchronization of the circadian biorhythms, the regulation of proliferation, apoptosis, oxidative phosphorylation, tumor growth, immune response, and neurodegenerative processes. This has prompted us consider whether these substances can substantially enhance the efficacy of targeted therapies in patients with advanced cancer diseases. Thus, despite the effectiveness of current malignancy therapies, these clinical approaches have adverse effects that decrease the patient’s quality of life and often result in therapy discontinuation. Thus, it is critical to avoid or reduce these harmful effects by introducing complementary treatments.

This Special Issue on “Melatonin and Vitamins: New Insights into Cancer Therapies” will include manuscripts on the latest scientific findings in terms of the molecular mechanisms of the actions and biological functions of melatonin and vitamins, including their metabolites. These papers aim to improve our understanding of the biological meaning of these substances, as well as the involved signaling pathways. Original experimental research, review articles, and commentary articles on this and related topics are invited.

Dr. Konrad Kleszczyński
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • melatonin
  • metabolites of melatonin
  • vitamin D
  • vitamins
  • melanoma
  • skin diseases
  • cell signaling
  • targeted therapy
  • dermatoendocrinology
  • natural products

Published Papers (2 papers)

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Research

17 pages, 2505 KiB  
Article
Fibroblast Growth Factor Receptor Inhibitors Decrease Proliferation of Melanoma Cell Lines and Their Activity Is Modulated by Vitamin D
by Anna Piotrowska, Joanna I. Nowak, Justyna M. Wierzbicka, Paweł Domżalski, Monika Górska-Arcisz, Rafał Sądej, Delfina Popiel, Maciej Wieczorek and Michał A. Żmijewski
Int. J. Mol. Sci. 2024, 25(5), 2505; https://doi.org/10.3390/ijms25052505 - 21 Feb 2024
Viewed by 649
Abstract
Regardless of the unprecedented progress in malignant melanoma treatment strategies and clinical outcomes of patients during the last twelve years, this skin cancer remains the most lethal one. We have previously documented that vitamin D and its low-calcaemic analogues enhance the anticancer activity [...] Read more.
Regardless of the unprecedented progress in malignant melanoma treatment strategies and clinical outcomes of patients during the last twelve years, this skin cancer remains the most lethal one. We have previously documented that vitamin D and its low-calcaemic analogues enhance the anticancer activity of drugs including a classic chemotherapeutic—dacarbazine—and an antiangiogenic VEGFRs inhibitor—cediranib. In this study, we explored the response of A375 and RPMI7951 melanoma lines to CPL304110 (CPL110), a novel selective inhibitor of fibroblast growth factor receptors (FGFRs), and compared its efficacy with that of AZD4547, the first-generation FGFRs selective inhibitor. We also tested whether 1,25(OH)2D3, the active form of vitamin D, modulates the response of the cells to these drugs. CPL304110 efficiently decreased the viability of melanoma cells in both A375 and RPMI7951 cell lines, with the IC50 value below 1 µM. However, the metastatic RPMI7951 melanoma cells were less sensitive to the tested drug than A375 cells, isolated from primary tumour site. Both tested FGFR inhibitors triggered G0/G1 cell cycle arrest in A375 melanoma cells and increased apoptotic/necrotic SubG1 fraction in RPMI7951 melanoma cells. 1,25(OH)2D3 modulated the efficacy of CPL304110, by decreasing the IC50 value by more than 4-fold in A375 cell line, but not in RPMI7951 cells. Further analysis revealed that both inhibitors impact vitamin D signalling to some extent, and this effect is cell line-specific. On the other hand, 1,25(OH)2D3, have an impact on the expression of FGFR receptors and phosphorylation (FGFR-Tyr653/654). Interestingly, 1,25(OH)2D3 and CPL304110 co-treatment resulted in activation of the ERK1/2 pathway in A375 cells. Our results strongly suggested possible crosstalk between vitamin D-activated pathways and activity of FGFR inhibitors, which should be considered in further clinical studies. Full article
(This article belongs to the Special Issue Melatonin and Vitamins: New Insights into Cancer Therapies)
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17 pages, 3339 KiB  
Article
Melanogenesis Is Directly Affected by Metabolites of Melatonin in Human Melanoma Cells
by Jack K. S. Möller, Kinga Linowiecka, Maciej Gagat, Anna A. Brożyna, Marek Foksiński, Agnieszka Wolnicka-Glubisz, Elżbieta Pyza, Russel J. Reiter, Meri K. Tulic, Andrzej T. Slominski, Kerstin Steinbrink and Konrad Kleszczyński
Int. J. Mol. Sci. 2023, 24(19), 14947; https://doi.org/10.3390/ijms241914947 - 06 Oct 2023
Viewed by 1318
Abstract
Melatonin (N-acetyl-5-methoxytryptamine, MEL), its kynurenic (N1-acetyl-N2-formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, produced by the pineal gland, brain and peripheral organs, displays a diversity of [...] Read more.
Melatonin (N-acetyl-5-methoxytryptamine, MEL), its kynurenic (N1-acetyl-N2-formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, produced by the pineal gland, brain and peripheral organs, displays a diversity of physiological functions including anti-inflammatory, immunomodulatory, and anti-tumor capacities. Herein, we assessed their regulatory effect on melanogenesis using amelanotic (A375, Sk-Mel-28) and highly pigmented (MNT-1, melanotic) human melanoma cell lines. We discovered that subjected compounds decrease the downstream pathway of melanin synthesis by causing a significant drop of cyclic adenosine monophosphate (cAMP) level, the microphthalmia-associated transcription factor (MITF) and resultant collapse of tyrosinase (TYR) activity, and melanin content comparatively to N-phenylthiourea (PTU, a positive control). We observed a reduction in pigment in melanosomes visualized by the transmission electron microscopy. Finally, we assessed the role of G-protein-coupled seven-transmembrane-domain receptors. Obtained results revealed that nonselective MT1 and MT2 receptor antagonist (luzindole) or selective MT2 receptor antagonist (4-P-PDOT) did not affect dysregulation of the melanin pathway indicating a receptor-independent mechanism. Our findings, together with the current state of the art, provide a convenient experimental model to study the complex relationship between metabolites of melatonin and the control of pigmentation serving as a future and rationale strategy for targeted therapies of melanoma-affected patients. Full article
(This article belongs to the Special Issue Melatonin and Vitamins: New Insights into Cancer Therapies)
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