Abstract
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 language | English (US) |
|---|---|
| Pages (from-to) | 347-348 |
| Number of pages | 2 |
| Journal | Anti-Cancer Agents in Medicinal Chemistry |
| Volume | 16 |
| Issue number | 3 |
| State | Published - Mar 1 2016 |
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Keywords
- Angiogenesis
- Breast neoplasms
- Cell hypoxia
- Cell line
- Gene expression
- Melatonin
- Vascular endothelial growth factors
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Cancer Research
Cite this
Melatonin regulates angiogenic factors under hypoxia in breast cancer cell lines. / Jardim-Perassi, Bruna Victorasso; Lourenço, Mateus Repolês; Doho, Gabriel Mandarini; Grígolo, Ingrid Helen; Gelaleti, Gabriela Bottaro; Ferreira, Lívia Carvalho; Borin, Thaiz Ferraz; Moschetta, Marina Gobbe; de Campos Zuccari, Debora Aparecida Pires.
In: Anti-Cancer Agents in Medicinal Chemistry, Vol. 16, No. 3, 01.03.2016, p. 347-348.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Melatonin regulates angiogenic factors under hypoxia in breast cancer cell lines
AU - Jardim-Perassi, Bruna Victorasso
AU - Lourenço, Mateus Repolês
AU - Doho, Gabriel Mandarini
AU - Grígolo, Ingrid Helen
AU - Gelaleti, Gabriela Bottaro
AU - Ferreira, Lívia Carvalho
AU - Borin, Thaiz Ferraz
AU - Moschetta, Marina Gobbe
AU - de Campos Zuccari, Debora Aparecida Pires
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Breast neoplasms
KW - Cell hypoxia
KW - Cell line
KW - Gene expression
KW - Melatonin
KW - Vascular endothelial growth factors
UR - http://www.scopus.com/inward/record.url?scp=84958986256&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958986256&partnerID=8YFLogxK
M3 - Article
C2 - 25963143
AN - SCOPUS:84958986256
VL - 16
SP - 347
EP - 348
JO - Anti-Cancer Agents in Medicinal Chemistry
JF - Anti-Cancer Agents in Medicinal Chemistry
SN - 1871-5206
IS - 3
ER -