New platinum(II) complexes containing both an O,O′-chelated acetylacetonate ligand and a sulfur ligand in the platinum coordination sphere induce apoptosis in HeLa cervical carcinoma cells

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

“…which the activity appears to be associated both with its intracellular accumulation and with the formation of DNA adducts [6,7], the cytotoxicity of this new compound is related to the intracellular accumulation only, showing a low reactivity with nucleobases and a specific reactivity with sulphur ligands, suggesting that the cellular targets could be amino acid residues of proteins. The different mechanism of action of the new complex, having biological targets, different from those of cisplatin, may render it intrinsically able to evoke less chemo-resistance.…”

“…PKC-ε can be involved in ERK1/2 activation at several levels of the classical M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 MAPK cascade [53], including the direct interaction with MEK [54]. In HeLa cells, [Pt(O,O'-acac)(γ-acac)(DMS)] induced ERK1/2 activation through PKCs [6]. Also, PKCs pathways regulate cell death by both cisplatin [55] and [Pt(O,O'-acac)(γ-acac)(DMS)] [6].…”

“…In HeLa cells, [Pt(O,O'-acac)(γ-acac)(DMS)] induced ERK1/2 activation through PKCs [6]. Also, PKCs pathways regulate cell death by both cisplatin [55] and [Pt(O,O'-acac)(γ-acac)(DMS)] [6]. In thyroid PC Cl3 cell line, PKC-ε has a role in the apoptosis-signalling pathways caused by many stimuli [56]; in these cells PKC-ε also mediates the apoptotic effects of cisplatin through p38MAPK activity [8].…”

“…Recently, a platinum complex containing two acetylacetonate ligands, one O,O'-chelate and the other sigma-linked by methionine in the gamma position, and dimethylsulphide (DMS) in the metal coordination sphere has been synthesized [5] and shown to exhibit interesting biological activities [6][7][8][9].Differently from cisplatin, for which the activity appears to be associated both with its intracellular accumulation and with the formation of DNA adducts [6,7], the cytotoxicity of this new compound is related to the intracellular accumulation only, showing a low reactivity with nucleobases and a specific reactivity with sulphur ligands, suggesting that the cellular targets could be amino acid residues of proteins. The different action mechanism of the new complex, having different biological targets, with respect to cisplatin, may render it intrinsically able to evoke less A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 compared with cisplatin, [Pt(O,O'-acac)(γ-acac)(DMS)] induces less severe changes on fundamental events of neuroarchitecture development, such as no high apoptotic events, less altered granule cell migration and Purkinje cell dendrite growth, suggesting a low neurotoxicity for normal central nervous system [10].…”

Effects of cisplatin on matrix metalloproteinase-2 in transformed thyroid cells

“…Each sample was mixed with equal amounts of SDS sample buffer and electrophoresed on 10% polyacrylamide gels containing 1 mg/ml gelatin as the protease substrate. Following electrophoresis, gels were placed in Triton A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 5 -Urso et al Effects of cisplatin on MMP-2 X-100 solution (50 mM Tris/HCl pH 7.4, containing 2.5% Triton X-100) for 1 h to remove SDS, and then incubated for [16][17][18] h at 37°C in developing buffer (50 mM Tris base, 200 mM NaCl, 5 mM CaCl 2 , and 1% Triton X-100, pH 7,4). After incubation, gels were stained in 30% methanol, 10% acetic acid, and 0.5% w/v coomassie brilliant blue for 1 h followed by destaining.…”