The Effects of Newly Synthesized Platinum(IV) Complexes on Cytotoxicity and Radiosensitization of Human Tumour CellsIn Vitro

Abstract

Aim: Newly synthesized platinum(IV) complexes with ethylenediamine-N,N'-diacetate ligands (EDDA-type) (butyl-Pt and pentyl-Pt) were investigated against two cancer (A549 lung, and HTB 140 melanoma) and one noncancerous (MRC-5 embryonic lung fibroblast) human cell lines. Materials and Methods: The effects of these agents were compared with those of cisplatin after 6-, 24-and 48-h treatment. Sulforhodamine-B (SRB) assay was performed to estimate the cytotoxic effect, while the inhibitory effect on cell proliferation was measured using 5-bromo-2,deoxyuridine (BrdU) incorporation assay. Cell cycle analysis was performed by flow cytometry. Type of cell death induced by these agents was determined by electrophoretic analysis of DNA, flow cytometry and by western blot analysis of proteins involved in induction of apoptosis. The effects of gamma irradiation, alone and in combination with platinumbased compounds, were examined by clonogenic and SRB assays. Results: All examined platinum-based compounds had inhibitory and antiproliferative effects on A549 cells, but not on HTB140 and MRC-5 cells. Butyl-Pt, pentyl-Pt and cisplatin arrested the cell cycle in the S-phase and induced apoptotic cell death via regulation of expression of B-cell lymphoma 2 (BCL2) and BCL2-associated X (BAX) proteins. Platinum-based compounds increased the sensitivity of A549 cells to gamma irradiation. Butyl-Pt and pentyl-Pt showed better antitumour effects against A549 cells than did cisplatin, by interfering in cell proliferation and the cell cycle, and by triggering apoptosis. Conclusion: The effects of gamma irradiation on tumour cells may be amplified by pre-treatment of cells with platinum-based compounds.Cisplatin or cis-diamminedichloroplatinum(II) is an effective chemotherapeutic agent that is used in nearly 50% of all patients with cancer (1). It has been used in the fight against ovarian, head and neck, bladder, cervical, oesophageal, as well as against small-cell and non-small-cell lung cancer. The clinical utility of cisplatin is based on the inhibition of the processes that are important for growth and proliferation of cancer cells by binding to DNA molecules and preventing replication, transcription and cell-cycle progression, leading to tumour cell death (2, 3). However, cisplatin administration is associated with adverse effects and therapy resistance. The development of platinum analogues that have similar effectiveness as cisplatin but better toxicity profiles and lack cross-resistance is the major concern in research centres worldwide. Different modifications of cisplatin have been investigated to achieve this aim.Platinum complexes are widely used in cancer therapy research. Approximately 30 platinum(II) and platinum(IV) 5001

Antitumor Activity of Palladium(II) Complexes on DU-145 Cell Line in Vitro

“…In the area of non-platinum complexes, various complexes containing gold, copper, ruthenium, and palladium have shown a strong cytotoxic effect on different cancer cell lines (6)(7)(8)(9). Also, many of these non-platinum complexes showed a high degree of selectivity which means they had a low effect on the viability of healthy cells in vitro (10)(11)(12). Therefore, transition metals represent the future in the treatment of different types of cisplatin-resistant cancer.…”

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

“…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.…”

“…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).…”

“…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 0 -diacetate)-a type of ligands had considerable effects on various cancer cell lines with promising potential to overcome cisplatin-resistance (Dimitrijevi c et al, 2013;Juriševi c et al, 2016;Petrovi c et al, 2020;Stojkovi c et al, 2014).…”