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Thyroid hormones derivatives reduce proliferation and induce cell death and DNA damage in ovarian cancer

Elena Shinderman-Maman1,2,3, Keren Cohen1,2,3, Dotan Moskovich1,2,3

  • 1Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, Israel.

Scientific Reports
|November 30, 2017
PubMed

Insights

Natural thyroid hormone derivatives like tetrac, triac, and T1AM show cytotoxic potential against ovarian cancer. These compounds inhibit proliferation and induce apoptosis, offering a promising new therapeutic avenue for this aggressive disease.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Ovarian cancer is an aggressive malignancy requiring novel therapeutic strategies.
  • Thyroid hormones binding to αvβ3 integrin promote ovarian cancer growth.
  • Natural thyroid hormone derivatives may antagonize these growth-promoting actions.

Purpose of the Study:

  • To investigate the potential of thyroid hormone derivatives (tetrac, triac, T1AM) as novel ovarian cancer treatments.
  • To evaluate their effects on cell proliferation, apoptosis, and DNA damage in ovarian cancer cells.
  • To explore the role of αvβ3 integrin in their mechanism of action.

Main Methods:

  • Studied the effects of tetrac, triac, and T1AM on OVCAR3 and A2780 ovarian cancer cell lines, CHOK1 control cells, and HEK293 cells (αvβ3-deficient or transfected).
  • Assessed cell proliferation, apoptosis (using annexin-PI, SubG1/cell-cycle analysis, apoptotic gene expression, caspase-3 and PARP-1 cleavage), and DNA damage markers (ATM, PARP-1).
  • Investigated integrin involvement using αvβ3-transfected HEK293 cells and employed a pan-caspase inhibitor to assess caspase-dependent/independent apoptosis.

Main Results:

  • Differential inhibition of cell proliferation was observed in ovarian cancer cells compared to control cells.
  • Apoptosis was induced in ovarian cancer cells, confirmed by multiple assays, and partially reversed by a pan-caspase inhibitor, suggesting both caspase-dependent and -independent pathways.
  • Induction of DNA damage response proteins (ATM, PARP-1) and apoptosis-inducing factor (AIF) was observed in ovarian cancer cells.
  • Integrin αvβ3 involvement was demonstrated in the apoptotic effects of triac and T1AM.

Conclusions:

  • Tetrac, triac, and T1AM exhibit significant cytotoxic potential against ovarian cancer cells.
  • These thyroid hormone derivatives demonstrate anti-proliferative and pro-apoptotic effects, targeting key cellular pathways.
  • The findings suggest that these compounds represent a promising novel therapeutic approach for ovarian cancer, potentially involving αvβ3 integrin.
  • Further investigation into these natural thyroid hormone derivatives is warranted for ovarian cancer treatment development.

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