Ruthenium(II) complexes as mitochondrial inhibitors of topoisomerase induced A549 cell apoptosis

Tang, Heng Yuan; Guo, Xinhua; Yu, Wenzhu; Gao, Jie; Zhu, Xufeng; Huang, Zunnan; Ou, Wei; Zhang, Hanfu; Chen, Lanmei; Chen, Jincan

doi:10.1016/j.jinorgbio.2023.112295

Cited by 3 publications

(2 citation statements)

References 55 publications

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“…In comparison to the control, a higher amount of JC-1 monomer indicative of MMP depolarization is found with Ru-IM treatment. This trend has also been reported for other ruthenium compounds active against lung and liver cancer cell lines.…”

Section: Resultssupporting

confidence: 82%

Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound

Nayeem,

Sauma,

Ahad

et al. 2024

ACS Pharmacol. Transl. Sci.

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Triple negative breast cancer (TNBC) represents a subtype of breast cancer that does not express the three major prognostic receptors of human epidermal growth factor receptor 2 (HER2), progesterone (PR), and estrogen (ER). This limits treatment options and results in a high rate of mortality. We have reported previously on the efficacy of a water-soluble, cationic organometallic compound (Ru-IM) in a TNBC mouse xenograft model with impressive tumor reduction and targeted tumor drug accumulation. Ru-IM inhibits cancer hallmarks such as migration, angiogenesis, and invasion in TNBC cells by a mechanism that generates apoptotic cell death. Ru-IM displays little interaction with DNA and appears to act by a P53-independent pathway. We report here on the mitochondrial alterations caused by Ru-IM treatment and detail the inhibitory properties of Ru-IM in the PI3K/AKT/mTOR pathway in MDA-MB-231 cells. Lastly, we describe the results of an efficacy study of the TNBC xenografted mouse model with Ru-IM and Olaparib monotherapy and combinatory treatments. We find 59% tumor shrinkage with Ru-IM and 65% with the combination. Histopathological analysis confirmed no test-article-related toxicity. Immunohistochemical analysis indicated an inhibition of the angiogenic marker CD31 and increased levels of apoptotic cleaved caspase 3 marker, along with a slight inhibition of p-mTOR. Taken together, the effects of Ru-IM in vitro show similar trends and translation in vivo. Our investigation underscores the therapeutic potential of Ru-IM in addressing the challenges posed by TNBC as evidenced by its robust efficacy in inhibiting key cancer hallmarks, substantial tumor reduction, and minimal systemic toxicity.

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Section: Resultssupporting

confidence: 82%

Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound

Nayeem,

Sauma,

Ahad

et al. 2024

ACS Pharmacol. Transl. Sci.

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“…Preliminary data in the literature suggest that ruthenium compounds might be good candidate agents against cancer cells. [26][27][28][29] Studies over the year suggested that ruthenium has anticancer activity against various cancer cells including breast, 30 lung, 31 prostate, and ovarian cells. 13 In this study, eight different novel ruthenium complexes were synthesized and their anticancer potential against MCF-7 cells was studied.…”

Section: Pharmacology/biologymentioning

confidence: 99%

Ruthenium compounds: Are they the next‐era anticancer agents?

Kavukcu,

Özverel,

Kıyak

et al. 2024

Applied Organom Chemis

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This study focuses on the cytotoxic activity of ruthenium(II) complexes, denoted as Ru1–8, which exhibit coordination with nitrogen (amine and amide), oxygen, and sulfur donor atoms, coupled with aryl and aliphatic wingtips. Specifically, the complexes were evaluated for their impact on the MCF‐7 breast cancer cell line. A systematic exploration of various parameters, including solubility, donor atom type, metal number, carbon chain length, aromatic ring presence, and molecular weight, was conducted to discern their influence on cytotoxic activity. The investigation involved assessing the cell viability across five concentrations (100, 50, 25, 10, and 5 μM) for five distinct monometallic and three bimetallic ruthenium complexes. Notably, Ru3, characterized by an extended carbon chain length (dodecyl) and favorable oil solubility facilitating cellular membrane penetration, demonstrated particularly promising results with the IC50 value of 1.03 μM. This research underscores the critical role of ligand design in shaping the cytotoxic potential of ruthenium(II) complexes and emphasizes the suitability of the Ru(II) p‐cymene complexes, as demonstrated by their robust activity against breast cancer in this specific investigation.

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Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death

Neves,

Bomfim,

Kataura

et al. 2024

Biomedicine & Pharmacotherapy

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Ruthenium(II) complexes as mitochondrial inhibitors of topoisomerase induced A549 cell apoptosis

Cited by 3 publications

References 55 publications

Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound

Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound

Ruthenium compounds: Are they the next‐era anticancer agents?

Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death

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