RT Journal Article SR Electronic T1 The Effects of Newly Synthesized Platinum(IV) Complexes on Cytotoxicity and Radiosensitization of Human Tumour Cells In Vitro JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 5001 OP 5013 DO 10.21873/anticanres.14503 VO 40 IS 9 A1 MARIJA PETROVIC A1 SUZANA POPOVIC A1 DEJAN BASKIC A1 MILOS TODOROVIC A1 PREDRAG DJURDJEVIC A1 ALEKSANDRA RISTIC-FIRA A1 OTILIJA KETA A1 VLADANA PETKOVIC A1 LELA KORICANAC A1 DANIJELA STOJKOVIC A1 VERICA JEVTIC A1 SRECKO TRIFUNOVIC A1 DANIJELA TODOROVIC YR 2020 UL http://ar.iiarjournals.org/content/40/9/5001.abstract AB 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 non-cancerous (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 platinum-based 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.