BIBLIOS

Document type
Journal articles

Document subtype
Full paper

Title
Calcium acts as a central player in melatonin antitumor activity in sarcoma cells

Participants in the publication
Ana M. Sánchez-Sánchez (Author)
María Turos-Cabal (Author)
Noelia Puente-Moncada (Author)
Federico Herrera (Author)
Dep. Química e Bioquímica
BioISI
Carmen Rodríguez (Author)
Vanesa Martín (Author)

Summary
\n\nPurpose: Chondrosarcoma and osteosarcoma are the most frequently occurring bone cancers. Although surgery and chemotherapy are currently clinically applied, improved treatment options are urgently needed. Melatonin is known to inhibit cell proliferation in both tumor types. Although the underlying mechanisms are not clear yet, calcium homeostasis has been reported to be a key factor in cancer biology. Here, we set out to investigate whether regulation of calcium by this indolamine may be involved in its antitumor effect.\n\nMethods: Cell viability was measured using a MTT assay and flow cytometry was used to measure levels of cytosolic calcium, intracellular oxidants, mitochondrial membrane potential and cell cycle progression. Mitochondrial calcium was analyzed by fluorimetry. Cell migration was determined using a scratch wound-healing assay. Western blot analysis was used to assess the expression of proteins related to cell cycle progression, epithelial to mesenchymal transition (EMT), Ac-CoA synthesis and intracellular signaling pathways.\n\nResults: We found that melatonin decreases cytosolic and mitochondrial Ca2+ levels, intracellular oxidant levels, mitochondrial function and the expression of the E1 subunit of the pyruvate dehydrogenase complex. These changes were found to be accompanied by decreases in cell proliferation, cell migration and EMT marker expression. The addition of CaCl2 prevented the changes mentioned above, while co-treatment with the calcium chelator BAPTA enhanced the effects.\n\nConclusions: Our data indicate that regulation of calcium homeostasis is a key factor in the inhibition of cell proliferation and migration by melatonin. This effect should be taken into consideration in combined therapies with traditional or new antitumor compounds, since it may circumvent therapy resistance.


Institution
BioISI - Biosystems & Integrative Sciences Institute

Where published
Cellular Oncology

Publication Identifiers
ISSN - 2211-3428

Publisher
Springer Science and Business Media LLC



Document Identifiers
DOI - https://doi.org/10.1007/s13402-022-00674-9
URL - http://dx.doi.org/10.1007/s13402-022-00674-9

Rankings
SCIMAGO Q1 (2023) - 1.326 - Molecular Medicine
SCIMAGO Q1 (2023) - 1.326 - Medicine (Miscellaneous)
SCIMAGO Q1 (2023) - 1.326 - Oncology

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