Melatonin regulates angiogenic factors under hypoxia in breast cancer cell lines

Bruna Victorasso Jardim-Perassi, Mateus Repolês Lourenço, Gabriel Mandarini Doho, Ingrid Helen Grígolo, Gabriela Bottaro Gelaleti, Lívia Carvalho Ferreira, Thaiz Ferraz Borin, Marina Gobbe Moschetta, Debora Aparecida Pires de Campos Zuccari

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Angiogenesis is the process of new blood vessel formation, regulated by a number of pro- and antiangiogenic factors and usually begins in response to hypoxia. Exogenous administration of melatonin has shown numerous anti-tumor effects and appears to inhibit tumor angiogenesis. However, many factors involved in the anti-angiogenic effect of melatonin are still under investigation. Here, we evaluate the effects of melatonin on cell viability and expression of angiogenic factors in MCF-7 and MDA-MB-231 breast cancer cells under hypoxic conditions. Cell viability was investigated by MTT and gene and protein expression of the hypoxia-inducible factor-1a (HIF-1α) and vascular endothelial growth factor (VEGF-A) were verified by qPCR and immunocytochemistry after melatonin treatment (1 mM) under hypoxic conditions. Additionally, a protein array with 20 different cytokines/factors was performed on tumor cell lysates. The results showed that 1 mM of melatonin reduced the viability of MCF-7 and MDA-MB-231 cells (p < .05). This treatment also decreased both gene and protein expression of HIF-1a and VEGF-A under hypoxic conditions (p < .05). Among the proteins evaluated by protein array, melatonin treatment during hypoxia reduced VEGF-C, VEGFR receptors (VEGFR2 and VEGFR3), matrix metalloproteinase 9 (MMP9) and Angiogenin in MCF-7 cells. In MDA-MB-231 cells, a significant decrease was observed in VEGFR2, epidermal growth factor receptor (EGFR) and Angiogenin (p < .05). Taken together, these results showed that melatonin acts in the regulation of angiogenic factors in breast tumor cells and suggests an anti-angiogenic activity, particularly under hypoxic conditions.

Original languageEnglish (US)
Pages (from-to)347-348
Number of pages2
JournalAnti-Cancer Agents in Medicinal Chemistry
Issue number3
StatePublished - Mar 1 2016


  • Angiogenesis
  • Breast neoplasms
  • Cell hypoxia
  • Cell line
  • Gene expression
  • Melatonin
  • Vascular endothelial growth factors

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Cancer Research


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