Inhibition of cancer cell growth by ruthenium complexes

Iida, Joji; Bell-Loncella, Elisabeth T.; Purazo, Marc L.; Lu, Yifeng; Dorchak, Jesse; Clancy, R. L.; Slavik, Julianna; Cutler, Mary Lou; Shriver, Craig D.

doi:10.1186/s12967-016-0797-9

Cited by 33 publications

(20 citation statements)

References 45 publications

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“…Thus, complex (2) was selected to be further investigated using in vitro and in vivo assays. In accordance with our results, another study using a ruthenium arene o-PDA complex, [(p-cym)Ru(o-pda)Cl]PF 6 (o-PDA), demonstrates that after 48 h of incubation the inhibition of the proliferation of MDA-MB-231 cells (83 μM) was more than three times higher than in MCF-10A cells (> 260 μM) showing that it also exhibits selectivity for tumor cells [46]. Different studies have shown that ruthenium complexes with similar structure to the complex (2) also have cytotoxic activity against different tumor cells.…”

Section: In Vitro Assayssupporting

confidence: 91%

The trans -[Ru(PPh 3 ) 2 ( N , N -dimethyl- N ′-thiophenylthioureato-k 2 O,S)(bipy)]PF 6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo

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Plutı́n

et al. 2018

Journal of Inorganic Biochemistry

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Triple negative breast cancer (TNBC) is a heterogeneous subtype of breast tumors that does not exhibit the expression of estrogen and progesterone receptors, neither the amplification of the human epidermal growth factor receptor 2 (HER-2) gene. Despite all the advances in cancer treatments, the development of new anticancer drugs for TNBC tumors is still a challenge. There is an increasing interest in new agents to be used in cancer treatment. Ruthenium is a metal that has unique characteristics and important in vivo and in vitro results achieved for cancer treatment. Thus, in this work, with the aim to develop anticancer drugs, three new ruthenium complexes containing acylthiourea ligands have been synthesized and characterized: trans-[Ru(PPh)(N,N-dibutyl-N'-benzoylthioureato-kO,S)(2,2'-bipyridine (bipy))]PF(1), trans-[Ru(PPh)(N,N-dimethyl-N'-thiophenylthioureato-kO,S)(bipy)]PF(2) and trans-[Ru(PPh)(N,N-dimethyl-N'-benzoylthioureato-kO,S)(bipy)]PF(3). Then, the cytotoxicity of these three new ruthenium complexes was investigated in TNBC MDA-MB-231 and in non-tumor MCF-10A cells. Complex (2) was the most selective complex and was chosen for further studies to verify its effects on cell morphology, adhesion, migration, invasion, induction of apoptosis and DNA damage in vitro, as well as its toxicity and capacity of causing DNA damage in vivo. Complex (2) inhibited proliferation, migration, invasion, adhesion, changed morphology and induced apoptosis, DNA damage and nuclear fragmentation of TNBC cells at lower concentrations compared to non-tumor MCF-10A cells, suggesting an effective action for this complex on tumor cells. Finally, complex (2) did not induce toxicity or caused DNA damage in vivo when low doses were administered to mice.

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Section: In Vitro Assayssupporting

confidence: 91%

The trans -[Ru(PPh 3 ) 2 ( N , N -dimethyl- N ′-thiophenylthioureato-k 2 O,S)(bipy)]PF 6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo

Becceneri

Popolin

Plutı́n

et al. 2018

Journal of Inorganic Biochemistry

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“…As one of the most promising alternatives to platinum-based chemotherapeutics are Ru(II) and Ru(III) complexes. They possess unique multifunctional biochemical properties and exhibit lower toxic effects than platinum-based chemotherapeutics [14,15]. In cancer cells, trivalent Ru complexes are speculated to be reduced by cellular reductants, e.g., ascorbates, to their more active divalent form.…”

Section: Introductionmentioning

confidence: 99%

Binding Kinetics of Ruthenium Pyrithione Chemotherapeutic Candidates to Human Serum Proteins Studied by HPLC-ICP-MS

et al. 2020

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The development of ruthenium-based complexes for cancer treatment requires a variety of pharmacological studies, one of them being a drug’s binding kinetics to serum proteins. In this work, speciation analysis was used to study kinetics of ruthenium-based drug candidates with human serum proteins. Two ruthenium (Ru) complexes, namely [(η6-p-cymene)Ru(1-hydroxypyridine-2(1H)-thionato)Cl] (1) and [(η6-p-cymene)Ru(1-hydroxypyridine-2(1H)-thionato)pta]PF6 (2) (where pta = 1,3,5-triaza-7-phosphaadamantane), were selected. Before a kinetics study, their stability in relevant media was confirmed by nuclear magnetic resonance (NMR). Conjoint liquid chromatography (CLC) monolithic column, assembling convective interaction media (CIM) protein G and diethylamino (DEAE) disks, was used for separation of unbound Ru species from those bound to human serum transferrin (Tf), albumin (HSA) and immunoglobulins G (IgG). Eluted proteins were monitored by UV spectrometry (278 nm), while Ru species were quantified by post-column isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). Binding kinetics of chlorido (1) and pta complex (2) to serum proteins was followed from 5 min up to 48 h after incubation with human serum. Both Ru complexes interacted mainly with HSA. Complex (1) exhibited faster and more extensive interaction with HSA than complex (2). The equilibrium concentration for complex (1) was obtained 6 h after incubation, when about 70% of compound was bound to HSA, 5% was associated with IgG, whereas 25% remained unbound. In contrast, the rate of interaction of complex (2) with HSA was much slower and less extensive and the equilibrium concentration was obtained 24 h after incubation, when about 50% of complex (2) was bound to HSA and 50% remained unbound.

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“…It can also activate Nrf2 pathway for apoptosis primarily through the activation of caspase [ 49 ]. Another important report suggest that Ru-arene complexes are promising anti-cancer drugs that inhibit progression and metastasis by blocking multiple processes of cancers [ 50 ]. These Ru-arene complexes also inhibited growth factor productions such as VEGF-A, PDGF-AA, and GM-CSF proteins at the transcriptional levels.…”

Section: Resultsmentioning

confidence: 99%

Flexible ligated ruthenium(II) self-assemblies sensitizes glioma tumor initiating cellsin vitro

et al. 2017

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The tumorigenic potentials of residual cancer stem-like cells within tumors represent limitations of current cancer therapies. Here, the authors describe the effects of synthesized flexible, ligated, supramolecular self-assembled chair type tetranuclear ruthenium (II) metallacycles (2–5) on glioblastoma and glioma stem like cells. These self-assemblies were observed to be selectively toxic to glioma cells and CD133-positive glioma stem like cells population. Of the self-assembled compounds tested, metallacycle 4 more efficiently induced glioma stem like cells death within a brain cancer cell population and simultaneously inhibited the formation of free-floating gliospheres by reducing the sphere size. Detailed cell death studies revealed that treatment with metallacycle 4 reduced mitochondrial membrane potentials (an indicator of apoptosis) of glioma stem like cells. These results shows the elimination of cancer stem-like cells using an appropriate ligand binding adaptor offers a potential means of developing metal-based compounds for the treatment of chemo-resistant tumors.

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Inhibition of cancer cell growth by ruthenium complexes

Cited by 33 publications

References 45 publications

The trans -[Ru(PPh 3 ) 2 ( N , N -dimethyl- N ′-thiophenylthioureato-k 2 O,S)(bipy)]PF 6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo

The trans -[Ru(PPh 3 ) 2 ( N , N -dimethyl- N ′-thiophenylthioureato-k 2 O,S)(bipy)]PF 6 complex has pro-apoptotic effects on triple negative breast cancer cells and presents low toxicity in vivo

Binding Kinetics of Ruthenium Pyrithione Chemotherapeutic Candidates to Human Serum Proteins Studied by HPLC-ICP-MS

Flexible ligated ruthenium(II) self-assemblies sensitizes glioma tumor initiating cellsin vitro

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