Platinum Complexes with Edda (Ethylenediamine -N, N - Diacetate) Ligands as Potential Anticancer Agents

Jurišević, Milena; Radosavljević, Gordana; Arsenijević, Aleksandar; Milovanovic, Marija; Gajovic, Nevena; Djordjevic, Dragana; Milovanović, Jelena; Stojanović, Bojana; Ilić, Aleksandar; Sabo, Tibor J.; Kanjevac, Tatjana

doi:10.1515/sjecr-2016-0042

Cited by 7 publications

(6 citation statements)

References 61 publications

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“…The tested compounds show stronger activity in higher doses and long‐term exposure periods; however, they caused a significant reduction in the viability of the nonmalignant tested cell line. Interestingly, time and dose dependence were observed for all investigated compounds, but dependence on chain length was not detected as it was noted previously for platinum complexes with edda (ethylenediamine‐ N , N′ ‐diacetate) ligands by Jurišević et al (2016). Dimitrijević et al (2013) also reported that these compounds were much more potent than cisplatin, by evaluating their cytotoxic capacity on CLL (freshly isolated chronic lymphocytic leukemia cells).…”

Section: Discussionsupporting

confidence: 71%

“…Until now, about 30 new compounds entered some phase of the clinical trial. Yet, only a few have been introduced into clinical practice (Gibson, 2019; Jurišević et al, 2016; Petrović et al, 2020). Among others, Pt complexes with diamine ligands are in the field of interest as well.…”

Section: Introductionmentioning

confidence: 99%

“…Among others, Pt complexes with diamine ligands are in the field of interest as well. The literature data showed that Pt(II/IV) complexes with edda (ethylenediamine‐ N , N′ ‐diacetate)‐a type of ligands had considerable effects on various cancer cell lines with promising potential to overcome cisplatin‐resistance (Dimitrijević et al, 2013; Jurišević et al, 2016; Petrović et al, 2020; Stojković et al, 2014). Pt(IV) complexes with bidentate N , N′ ‐ligand precursors, O , O ′‐dialkyl esters (alkyl = ethyl, propyl, butyl) of ethylenediamine‐ N , N′ ‐di‐ S , S ‐(2,2′‐dibenzyl) acetic acid (Pt(IV) eddba complexes), used in this study, previously showed extremely stronger antiproliferative potential than cisplatin on freshly isolated chronic lymphocytic leukemia cells (Dimitrijević et al, 2013), but also high toxicity on female rat liver (Paunović et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Antiproliferative, antimigratory, and prooxidative potential of novel platinum( IV ) complexes and resveratrol on breast cancer ( MDA‐MB ‐231) and choriocarcinoma ( JEG ‐3) cell lines

et al. 2021

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Platinum(IV) complexes offer the potential to overcome cisplatin resistance of cancer cells, with possible improved selectivity. Resveratrol, a natural polyphenol with anticancer and antioxidant capacity, could limit the possible side effects of chemotherapeutics on healthy cells. This study investigates the effects of platinum(IV) complexes containing some esters of the ethylenediamine-N,N 0 -di-S,S-(2,2 0dibenzyl)acetate acid (H 2 -S,S-eddba), and resveratrol on proliferation, migration, and redox balance of breast cancer (MDA-MB-231), choriocarcinoma (JEG-3), and human lung fibroblast (MRC-5) cell line. According to IC 50 values, all complexes exhibited a significantly stronger antiproliferative effect on tested cell lines compared to cisplatin. Due to reduced adverse effects on MRC-5 cells, the complex containing ethyl-substituent (10 μM) was selected for further examination with resveratrol (25 μM) cotreatment. Resveratrol enhanced the survival of MRC-5 cells while diminished the viability of both used cancer cell lines when applied combined with selected complex. Furthermore, cotreatment of these two compounds decreased the migratory potential of tested cancer cell lines. The examined platinum(IV) complex was able to induce oxidative stress in all tested cell lines. Resveratrol proved to be efficient in protecting MRC-5 cells from complex-induced oxidative damage, while it significantly amplified antiproliferative, antimigratory, and prooxidative effects of platinum(IV) complex on both examined cancer cell lines. These findings may be valuable in elucidating the mechanism of action of platinum(IV) drugs, which should be further investigated.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antiproliferative, antimigratory, and prooxidative potential of novel platinum( IV ) complexes and resveratrol on breast cancer ( MDA‐MB ‐231) and choriocarcinoma ( JEG ‐3) cell lines

et al. 2021

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“…Large number of edda (ethylenediamine- N,N’ -diacetate)-type ligands and their corresponding platinum complexes have been successfully synthesized [ 11 , 12 ] and some of them showed significant cytotoxic effects [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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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“…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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Platinum Complexes with Edda (Ethylenediamine -N, N - Diacetate) Ligands as Potential Anticancer Agents

Cited by 7 publications

References 61 publications

Antiproliferative, antimigratory, and prooxidative potential of novel platinum( IV ) complexes and resveratrol on breast cancer ( MDA‐MB ‐231) and choriocarcinoma ( JEG ‐3) cell lines

Antiproliferative, antimigratory, and prooxidative potential of novel platinum( IV ) complexes and resveratrol on breast cancer ( MDA‐MB ‐231) and choriocarcinoma ( JEG ‐3) cell lines

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

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

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