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Ruthenium(II) Complex with 8-Hydroxyquinoline Exhibits Antitumor Activity in Breast Cancer Cell Lines.

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The ruthenium complex Ru(quin)2 shows promise as a novel breast cancer (BC) therapy, effectively killing cancer cells by inducing apoptosis, autophagy, and cell cycle arrest in both ER-positive and triple-negative BC models.

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Area of Science:

  • Medicinal Chemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Breast cancer (BC) is a leading cause of cancer-related death globally.
  • Limited treatment options and resistance to platinum-based drugs necessitate novel therapeutic strategies.
  • Developing regions face significant challenges in accessing advanced BC treatments.

Purpose of the Study:

  • To investigate the anticancer potential of the ruthenium complex Bis(quinolin-8-olato)bis(triphenylphosphine)ruthenium(II) (Ru(quin)2).
  • To evaluate Ru(quin)2 efficacy in both estrogen receptor-positive (ER-positive) and triple-negative breast cancer (TNBC) cell lines.
  • To elucidate the mechanisms of action underlying Ru(quin)2's cytotoxic effects.

Main Methods:

  • Cytotoxicity assays were performed on T47D (ER-positive) and MDA-MB-231 (TNBC) cell lines.
  • Apoptosis was assessed by measuring BAX expression, caspase-3 activity, Aurora B kinase levels, and histone release.
  • Autophagy was evaluated through LC3-I/LC3-II conversion and SQSTM1 levels, with involvement of MAPK signaling.
  • Cell cycle arrest was analyzed by quantifying cyclin D1, CDK4, CDK6, and p21 expression.

Main Results:

  • Ru(quin)2 exhibited dose-dependent cytotoxicity against both BC cell lines (IC50 values ~45-48 μM).
  • Cytotoxicity was mediated by apoptosis induction (increased BAX, caspase-3; decreased Aurora B, histone release).
  • Ru(quin)2 induced autophagy (LC3-II conversion, reduced SQSTM1) and G0/G1 cell cycle arrest (downregulated cyclins/CDKs, upregulated p21).

Conclusions:

  • Ru(quin)2 demonstrates significant anticancer activity through multiple mechanisms, including apoptosis, autophagy, and cell cycle arrest.
  • The ruthenium complex is a promising candidate for treating both ER-positive and triple-negative breast cancer.
  • Further in vivo studies are needed to explore its therapeutic potential and clinical applications.