Antileukemic action of novel diamine Pt(<scp>II</scp>) halogenido complexes: Comparison of the representative novel Pt(<scp>II</scp>) with corresponding Pt(<scp>IV</scp>) complex

Denčić, Sonja Misirlić; Poljarević, Jelena; Isakovic, Andjelka M.; Marković, Ivanka; Sabo, Tibor J.; Grgurić-Šipka, Sanja

doi:10.1111/cbdd.12945

Cited by 12 publications

(7 citation statements)

References 32 publications

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“…In accordance with these findings, it was recently established that DE-EDCP (50 μM) enhanced the superoxide anion production and inner mitochondrial membrane depolarization as evaluated by detection of phosphatidylserine externalization and DNA fragmentation due to apoptosis of HL-60 cells [ 16 ]. Pt(II) complex containing DE-EDCP induced HL-60 oxidative stress and apoptosis further evidenced by activation of initiator caspases (caspase-8 and caspase-9) [ 15 ]. On the other hand, Pt(IV) complex containing DE-EDCP causes oxidative stress-mediated necrotic death of glioma, melanoma and fibrosarcoma cells in vitro [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…The substance, O,O’ -diethyl-( S,S )-ethylenediamine- N,N’ -di-2-(3-cyclohexyl)propanoate dihydrochloride (compound marked as DE-EDCP, Figure 9 ), was synthesized according to previously described procedure [ 14 , 15 ] and registered as patent in Intellectual Property Office of the Republic of Serbia (Number 2015/11427-P-2013/0270). Cisplatin (cis-diamminedichloroplatinum(II)/cis-[PtCl 2 (NH 3 ) 2 ]) (Sigma-Aldrich) was used without purification.…”

Section: Methodsmentioning

confidence: 99%

“…It has been shown that platinum(IV) [ 14 ] and platinum(II) [ 15 ] complexes with cyclohexyl-functionailized ehylenediamine -N,N’ -diacetate-type ligand exhibit effective tumoricidal capacities against various cancer cell lines. The cytotoxic effects of these platinum complexes may be at least partly related to their organic ligands (ester derivatives of ( S,S )-ethylenediamine- N,N′- di-2-(3-cyclohexyl)propanoic acid).…”

Section: Introductionmentioning

confidence: 99%

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The organic esterO,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis

et al. 2018

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Pharmacological treatment of cancer is mostly limited by drug-toxicity and resistance. It has been noticed that new organic ester ligand, O,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride (named DE-EDCP) showed effective cytotoxic capacities against several human and mouse cancer cell lines. However, its effects on tumor growth and metastasis are unexplored. The aim of present study was to examine the ability of DE-EDCP to inhibit 4T1 murine breast cancer growth and progression and to explore possible molecular mechanisms. DE-EDCP exhibited significant tumoricidal activity on human and murine breast cancer cell lines. Further, marked reduction of murine breast cancer growth and progression by DE-EDCP was shown. DE-EDCP exhibits fewer side-effects compared to cisplatin as a conventional chemotherapeutic. Results obtained from in vivo and in vitro experiments indicate that DE-EDCP induces apoptosis and inhibits proliferation of 4T1 cells. DE-EDCP increases percentage of 4T1 cells in late apoptosis, expression of pro-apoptotic Bax and caspase-3, while decreases expression of anti-apoptotic Bcl-2. DE-EDCP treatment increased the percentage of TUNEL-positive nuclei and reduced Ki-67 expression in breast cancer tissue. DE-EDCP decreased expression of cyclin D3 and Ki-67, increased expression of cyclin-dependent kinase inhibitors p16, p21 and p27 and arrested 4T1 cells in G0/G1 cell cycle phase. Expression of STAT3 and downstream regulated molecules, NANOG and SOX2, was reduced in 4T1 cells after DE-EDCP treatment.In conclusion, DE-EDCP impairs breast cancer growth and progression by triggering cancer cell death and inhibition of cancer cell proliferation. DE-EDCP might be of interest in the development of the new anticancer agent.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The organic esterO,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis

et al. 2018

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“…Merenje aktivnosti kisele fosfataze je urađeno tačno kako je ranije opisano (10) i zasniva se na hidrolizi p-nitrofenil fosfata u kiseloj sredini dejstvom unutarćelijske kisele fosfataze, pri čemu se u živim ćelijama razvija žuto obojen rastvor porekla p-nitrofenola čija se apsorbanca meri na 405 nm automatskim čitačem mikrotitar ploča (Tecan Sunrise, Švajcarska) i direktno je proporcionalna broju živih ćelija.…”

Section: Određivanje Aktivnosti Kisele Fosfatazeunclassified

The effect of metformin on viability and mitochondrial status of tumor and non-tumor cell line

Ljubičić¹,

Pešić²,

Isakovic³

2022

Medicinski podmladak

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Introduction: Metformin is a drug of choice in the therapy of type II Diabetes mellitus. There is a growing evidence of metformin's antitumor activity, but the suggested mechanisms of such activity are still not fully elucidated. Aim: To investigate the effect of therapeutic doses of metformin on viability and mitochondrial status of human non-small cell lung carcinoma (NCI-H460) and human immortalized lung fibroblasts (MRC-5) cell lines. Material and methods: Acid phosphatase and Crystal Violet assays were used for the determination of NCI-H460 and MRC-5 cell viability after the treatment with metformin (10-60 µM) for 1-7 days. Mitochondrial membrane potential, production of reactive oxygen species and superoxide anion, as well as mitochondrial mass were measured using flow cytometry after the treatment of the cells for 3, 24 and 120 h, followed by staining with appropriate fluorochromes: JC-1, DHR, DHE and Mitotracker Red. Results: Metformin did not change the viability of both NCI-H460 and MRC-5 cells in all investigated time-points and all used concentrations. Depolarization of mitochondrial membrane was observed 3 h post-treatment in MRC-5 cells. Prolonged treatment (120 h) increased superoxide anion production and mitochondrial mass in NCI-H460 cells. No significant changes in production of reactive oxygen species were observed in both cells lines after short or extended exposure to metformin. Conclusion: : Therapeutic concentrations of metformin do not influence the viability of NCI-H460 and MRC-5 cells, but induce mitochondrial depolarization after short-term exposure in lung fibroblasts and increase production of superoxide anion and mitochondrial mass in lung carcinoma cells after prolonged treatment.

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“…17,20 It was found that generally they are less efficient than cisplatin. Opposite them, Pt IV complexes with esterifies edda-type ligands showed greater anticancer activity than corresponding Pt II complexes and cisplatin, [21][22][23] causing very rapid necrotic cell death in some cell lines.…”

Section: Introductionmentioning

confidence: 99%

Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP

Stanković

Ristić²,

Vukadinović

et al. 2018

Hum Exp Toxicol

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It was reported that novel O, O′-diethyl-(S, S)-ethylenediamine- N, N′-di-2-(3-cyclohexyl) propanoate dihydrochloride (DE-EDCP) displayed in vitro antiproliferative activity on several human and mouse cancer cell lines, which was comparable to that of the prototypical anticancer drug cisplatin. In order to reveal its toxicity profile, acute and repeated-dose toxicity studies were performed in Naval Medical Research Institute (NMRI) Han mice. The intravenous LD50 values of DE-EDCP were found to be 95.3 and 101.3 mg/kg body weight in female and male mice, respectively. In the subacute toxicity study, DE-EDCP was administered intravenously at the doses of 15, 25, and 40 mg/kg/day for a period of 28 days. There were no adverse effects on general condition, growth, feed and water consumption, and hematological parameters. There was a significant increase in urea and alanine aminotransferase in female mice and aspartate aminotransferase and alkaline phosphatase in both genders in 40 mg/kg/day dose-treated group. The histopathological changes confined to the liver and kidney, but in other organs were not found. Satellite group revealed that changes in the kidney and liver were less pronounced, suggesting their reversibility. Interactions with DNA could also be of importance for understanding DE-EDCP toxic side effects. Hyperchromic effect obtained with ultraviolet–visible, suggested electrostatic interactions between DE-EDCP and calf thymus DNA. The toxicity testing of DE-EDCP was conducted to predict human outcomes.

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Antileukemic action of novel diamine Pt(II) halogenido complexes: Comparison of the representative novel Pt(II) with corresponding Pt(IV) complex

Cited by 12 publications

References 32 publications

The organic esterO,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis

The organic esterO,O’-diethyl-(S,S)-ethylenediamine-N,N’-di-2-(3-cyclohexyl)propanoate dihydrochloride attenuates murine breast cancer growth and metastasis

The effect of metformin on viability and mitochondrial status of tumor and non-tumor cell line

Toxicity study of DE-EDCP as a potential drug for cancer therapy: Toxicity profile of DE-EDCP

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