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Updated: Aug 11, 2026
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
The oncostatic action of melatonin in an ovarian carcinoma cell line
J Petranka1, W Baldwin, J Biermann
1Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Abstract:
Melatonin is reported to reduce proliferation in many cell types, but the effect is small and the results are inconsistent. Information on the mechanism by which melatonin exerts its antiproliferative effects might provide insight into the variability of the response. In an ovarian adenocarcinoma cell line (BG-1), we find that melatonin at concentrations of 10(-9)-10(-7) M caused a 20-25% reduction in cell number. Melatonin also resulted in a similar reduction in [3H]-thymidine incorporation with no significant increase in cell death as measured by trypan blue incorporation. The Kd for melatonin reduction in cell number was approximately 5 x 10(-10) M. Melatonin ML2 receptors have a Kd for melatonin binding in the low nM range and are linked to the production of the calcium mobilizing agent inositol-1,4,5-trisphosphate (IP3). To investigate whether melatonin signaling involves an increase in cytosolic-free calcium. BG-1 cells were loaded with the calcium sensitive indicator, fura-2. Acute addition of melatonin (10(-5)-10(-9) M) did not alter cytosolic calcium. Addition of the putative nuclear receptor agonist CGP52608 caused a dose-dependent inhibition of cell number with a Kd of approximately 2 x 10(-9) M. Addition of CGP52608 caused a similar reduction in [3H]-thymidine incorporation. Neither melatonin (10(-8) M-10(-5) M) nor CGP52608 at concentrations below 10(-7) M induced cell death associated with the inhibition of cell proliferation; however, addition of CGP52608 at a high dose (10(-7) M) caused an increase in cell death, consistent with apoptosis. Growth inhibition by melatonin or CGP52608 did not alter the percentage of cells in G1 versus S/G2/M.
Insights
Melatonin and CGP52608 inhibit ovarian cancer cell proliferation by reducing cell number and DNA synthesis. This antiproliferative effect occurs without significant cell death, suggesting a cytostatic rather than cytotoxic mechanism.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Melatonin's antiproliferative effects are inconsistent across cell types.
- Understanding melatonin's mechanism is crucial for explaining response variability.
Purpose of the Study:
- Investigate melatonin's antiproliferative mechanism in ovarian adenocarcinoma cells.
- Determine if melatonin signaling involves cytosolic calcium changes.
Main Methods:
- Utilized BG-1 ovarian adenocarcinoma cell line.
- Measured cell number and [3H]-thymidine incorporation.
- Assessed cell death using trypan blue and monitored cytosolic calcium with fura-2.
Main Results:
- Melatonin (10(-9)-10(-7) M) reduced cell number and thymidine incorporation by 20-25%.
- CGP52608, a nuclear receptor agonist, also dose-dependently inhibited cell proliferation.
- Neither agent significantly increased cell death at effective concentrations, and cytosolic calcium levels remained unchanged.
Conclusions:
- Melatonin and CGP52608 exhibit cytostatic effects on ovarian cancer cells.
- The antiproliferative action does not appear to involve significant changes in cytosolic calcium.
- Further research into melatonin's nuclear receptor pathways is warranted.
