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Melatonin decreases estrogen receptor binding to estrogen response elements sites on the OCT4 gene in human breast cancer stem cells

View Article: PubMed Central - PubMed

ABSTRACT

Cancer stem cells (CSCs) pose a challenge in cancer treatment, as these cells can drive tumor growth and are resistant to chemotherapy. Melatonin exerts its oncostatic effects through the estrogen receptor (ER) pathway in cancer cells, however its action in CSCs is unclear. Here, we evaluated the effect of melatonin on the regulation of the transcription factor OCT4 (Octamer Binding 4) by estrogen receptor alpha (ERα) in breast cancer stem cells (BCSCs). The cells were grown as a cell suspension or as anchorage independent growth, for the mammospheres growth, representing the CSCs population and treated with 10 nM estrogen (E2) or 10 μM of the environmental estrogen Bisphenol A (BPA) and 1 mM of melatonin. At the end, the cell growth as well as OCT4 and ERα expression and the binding activity of ERα to the OCT4 was assessed. The increase in number and size of mammospheres induced by E2 or BPA was reduced by melatonin treatment. Furthermore, binding of the ERα to OCT4 was reduced, accompanied by a reduction of OCT4 and ERα expression. Thus, melatonin treatment is effective against proliferation of BCSCs in vitro and impacts the ER pathway, demonstrating its potential therapeutic use in breast cancer.

No MeSH data available.


MCF-7 cells grown in 3-dimensional method of mammospheres, treated with E2 or BPA with or without melatonin(A) Cell suspension treated for 6 days. (B) Anchorage Independent Growth (AIG) treated for 14 days. The magnification was 40 X.
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Figure 1: MCF-7 cells grown in 3-dimensional method of mammospheres, treated with E2 or BPA with or without melatonin(A) Cell suspension treated for 6 days. (B) Anchorage Independent Growth (AIG) treated for 14 days. The magnification was 40 X.

Mentions: To evaluate the effect of melatonin on mammospheres treated with BPA and E2, two methods of 3-dimensional growth were performed (cell suspension and AIG). For the cell suspension and AIG technique, the results were similar (Figure 1A, 1B). The treatment with 10 nM E2 and 10 μM BPA without melatonin significantly increased the number and the size of the mammospheres when compared with the control group (Figure 2A, 2B) in both technique. On the other hand, 1 mM of melatonin significantly decreased the number and size of mammospheres when compared with the control (Figure 2A, 2B). Furthermore, when the cells were stimulated by E2 or BPA and treated with melatonin concomitantly, there was a greater reduction in the number and size of mammospheres (Figure 2A, 2B).


Melatonin decreases estrogen receptor binding to estrogen response elements sites on the OCT4 gene in human breast cancer stem cells
MCF-7 cells grown in 3-dimensional method of mammospheres, treated with E2 or BPA with or without melatonin(A) Cell suspension treated for 6 days. (B) Anchorage Independent Growth (AIG) treated for 14 days. The magnification was 40 X.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979593&req=5

Figure 1: MCF-7 cells grown in 3-dimensional method of mammospheres, treated with E2 or BPA with or without melatonin(A) Cell suspension treated for 6 days. (B) Anchorage Independent Growth (AIG) treated for 14 days. The magnification was 40 X.
Mentions: To evaluate the effect of melatonin on mammospheres treated with BPA and E2, two methods of 3-dimensional growth were performed (cell suspension and AIG). For the cell suspension and AIG technique, the results were similar (Figure 1A, 1B). The treatment with 10 nM E2 and 10 μM BPA without melatonin significantly increased the number and the size of the mammospheres when compared with the control group (Figure 2A, 2B) in both technique. On the other hand, 1 mM of melatonin significantly decreased the number and size of mammospheres when compared with the control (Figure 2A, 2B). Furthermore, when the cells were stimulated by E2 or BPA and treated with melatonin concomitantly, there was a greater reduction in the number and size of mammospheres (Figure 2A, 2B).

View Article: PubMed Central - PubMed

ABSTRACT

Cancer stem cells (CSCs) pose a challenge in cancer treatment, as these cells can drive tumor growth and are resistant to chemotherapy. Melatonin exerts its oncostatic effects through the estrogen receptor (ER) pathway in cancer cells, however its action in CSCs is unclear. Here, we evaluated the effect of melatonin on the regulation of the transcription factor OCT4 (Octamer Binding 4) by estrogen receptor alpha (ERα) in breast cancer stem cells (BCSCs). The cells were grown as a cell suspension or as anchorage independent growth, for the mammospheres growth, representing the CSCs population and treated with 10 nM estrogen (E2) or 10 μM of the environmental estrogen Bisphenol A (BPA) and 1 mM of melatonin. At the end, the cell growth as well as OCT4 and ERα expression and the binding activity of ERα to the OCT4 was assessed. The increase in number and size of mammospheres induced by E2 or BPA was reduced by melatonin treatment. Furthermore, binding of the ERα to OCT4 was reduced, accompanied by a reduction of OCT4 and ERα expression. Thus, melatonin treatment is effective against proliferation of BCSCs in vitro and impacts the ER pathway, demonstrating its potential therapeutic use in breast cancer.

No MeSH data available.