Photoactive CO-releasing complexes containing iron – genotoxicity and ability in HO-1 gene induction in HL-60 cells

Wysokiński, Daniel; Lewandowska, Patrycja; Zątak, Daria; Juszczak, M.; Kluska, Magdalena; Lizińska, Daria; Rudolf, Bogna; Woźniak, Katarzyna

doi:10.1039/c9tx00070d

Cited by 6 publications

(8 citation statements)

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“…The HL-60 (human promyelocytic leukemia) cell line was obtained from the American Type Culture Collection (ATCC) and cultured as described previously 21 , 22 .…”

Section: Methodsmentioning

confidence: 99%

“…PBMCs and HL-60 cells were incubated with CORM-2 and iCORM-2 for 2 h at 37 °C in 5% CO 2 at 100 µM and then were washed and suspended in fresh IMDM medium preheated to 37 °C. DNA repair was assessed by the extent of residual DNA damage detected at each time-point using the comet assay as described previously 22 .…”

Section: Methodsmentioning

confidence: 99%

“…The comet assay was performed under alkaline conditions according to a procedure described previously 21 , 22 .…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was extracted from each sample after 3 h post-incubation without CORM-2 and iCORM-2. Reverse transcription and real-time PCR reaction were performed as described previously 22 .…”

Section: Methodsmentioning

confidence: 99%

“…After incubation in all the schemes, the cells were washed, suspended in LMP agarose and spread onto microscope slide. The slides were processed as described previously 21,22 .…”

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confidence: 99%

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DNA damage and antioxidant properties of CORM-2 in normal and cancer cells

Juszczak

Kluska

Wysokiński

et al. 2020

Sci Rep

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In this study, we compared the effect of tricarbonyldichlororuthenium (II) dimer (CORM-2) and its CO-depleted molecule (iCORM-2) on human peripheral blood mononuclear cells (PBMCs) and human promyelocytic leukemia HL-60 cells. We determined cell viability, DNA damage and DNA repair kinetics. We also studied the effect of both compounds on DNA oxidative damage, free radical level and HO-1 gene expression. We showed that at low concentrations both CORM-2 and iCORM-2 stimulate PBMCs viability. After 24-h incubation, CORM-2 and iCORM-2, at the concentration of 100 µM, reduce the viability of both PBMCs and HL-60 cells. We also demonstrated that CORM-2 and iCORM-2, in the 0.01-100 µM concentration range, cause DNA damage such as strand breaks and alkaline labile sites. DNA damage was repaired efficiently only in HL-60 cells. CORM-2 significantly reduces oxidative stress induced by 1 mM H 2 o 2 in normal and cancer cells. On the contrary, iCORM-2 in HL-60 cells increases the level of free radicals in the presence of 1 and 5 mM H 2 o 2. We also revealed that both CORM-2 and iCORM-2 induce HO-1 gene expression. However, CORM-2 induces this gene to a greater extent than iCORM-2, especially in HL-60 cells at 100 µM. Finally, we showed that CORM-2 and iCORM-2 reduce H 2 o 2-induced DNA oxidative damage. Furthermore, CORM-2 proved to be a compound with stronger antioxidant properties than iCORM-2. Our results suggest that both active CORM-2 and inactive iCORM-2 exert biological effects such as cyto-and genotoxicity, antioxidant properties and the ability to induce the HO-1 gene. The released CO as well as iCORM-2 can be responsible for these effects. Carbon monoxide (CO) is a colorless, tasteless and odorless gas produced by the burning of fuels and organic materials. It is reported to be the most frequent cause of fatal poisoning with an incidence rate of 31%. CO is readily absorbed and is unchanged by the lungs. CO demonstrates more than 200-fold stronger affinity for hemoglobin compared to oxygen. Therefore, even a small level of CO may cause poisoning. In contrast to hypoxiainducing toxic concentrations, a low dose of CO or even nanomolar concentrations exert biological activities. CO is produced in low amounts as a byproduct of normal human metabolism by the enzyme called heme oxygenase (HO-1) 1. CO has the ability to reduce the stimulation of guanylate cyclase to generate cyclic guanosine 3′,5′-monophosphate (cGMP). As a signaling molecule, CO modulates several p38 mitogen-activated protein kinase (MAPK)-related signaling pathways via both cGMP-dependent and independent processes, directly activates calcium-dependent potassium channels and induces protein kinase B (Akt) phosphorylation via the phosphatidylinositol 3-kinase/Akt pathway 2. Moreover, CO inhibits mitochondrial respiration by binding the ferrous heme a 3 in the active site of cyclooxygenase (COX), effectively shutting down oxidative phosphorylation, similar to the effects of cyanide and nitric oxide (NO) 3. The cGMP-dependent activity of CO includes inhibit...

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“…The HL-60 (human promyelocytic leukemia) cell line was obtained from the American Type Culture Collection (ATCC) and cultured as described previously 21 , 22 .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The comet assay was performed under alkaline conditions according to a procedure described previously 21 , 22 .…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was extracted from each sample after 3 h post-incubation without CORM-2 and iCORM-2. Reverse transcription and real-time PCR reaction were performed as described previously 22 .…”

Section: Methodsmentioning

confidence: 99%

“…After incubation in all the schemes, the cells were washed, suspended in LMP agarose and spread onto microscope slide. The slides were processed as described previously 21,22 .…”

mentioning

confidence: 99%

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DNA damage and antioxidant properties of CORM-2 in normal and cancer cells

Juszczak

Kluska

Wysokiński

et al. 2020

Sci Rep

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Cytotoxicity of piano‐stool ruthenium cyclopentadienyl complexes bearing different imidato ligands

Juszczak

Kluska

Kosińska

et al. 2022

Applied Organom Chemis

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In these studies, we investigated a cytotoxic and genotoxic potential of four ruthenium cyclopentadienyl complexes bearing different imidato ligands: (η5‐cyclopentadienyl)Ru (CO)2(η1‐N‐maleimidato) (1), (η5‐cyclopentadienyl)Ru (CO)2‐N‐methoxysuccinimidato (2), (η5‐cyclopentadienyl)Ru (CO)2‐N‐ethoxysuccinimidato (3), and (η5‐cyclopentadienyl)Ru (CO)2‐N‐phthalimidato (4). We used two types of cells—normal peripheral blood mononuclear cells (PBMCs) and leukemic HL‐60 cells. We observed that complex 1 was highly cytotoxic and genotoxic, both for normal and cancer cells at concentrations from 0.5 to 250 μM. Interestingly, complex 1 was 10 times more cytotoxic to HL‐60 cells compared with PBMCs. Complexes 2–4 were cytotoxic only for HL‐60 cells at the highest used concentrations. Furthermore, we observed an increase in the viability of PBMCs after incubation with succinimide complexes 2 and 3. We also showed that complex 1 arrested cell cycle in the sub‐G1 phase and induced apoptosis. We found that different properties of studied ruthenium complexes depend significantly on the type of imide ligand bind to the ruthenium atom. The density functional theory (DFT) calculation of maleimide and succinimide revealed some significant differences of these compounds that would be related to biological activity. Our results indicate that ruthenium complex 1 should be further investigated in detail for its anticancer properties.

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Brief survey of diiron and monoiron carbonyl complexes and their potentials as CO-releasing molecules (CORMs)

Jiang

Xiao

Zhong

et al. 2021

Coordination Chemistry Reviews

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Photoactive CO-releasing complexes containing iron – genotoxicity and ability in HO-1 gene induction in HL-60 cells

Abstract: This paper presents the results of research on the biological properties of two photoactive CO-releasing molecules containing iron, i.e. (η5-C5H5)Fe(CO)2(η1-N-maleimidato) (complex A) and (η5-C5H5)Fe(CO)2(η1-N-succinimidato) (complex B).

Cited by 6 publications

References 47 publications

DNA damage and antioxidant properties of CORM-2 in normal and cancer cells

DNA damage and antioxidant properties of CORM-2 in normal and cancer cells

Cytotoxicity of piano‐stool ruthenium cyclopentadienyl complexes bearing different imidato ligands

Brief survey of diiron and monoiron carbonyl complexes and their potentials as CO-releasing molecules (CORMs)

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