RESUMEN
Two new mono-nuclear heteroleptic platinum(II) complexes, [Pt(bpy)(iip)](PF6)2 (1) and [Pt(bpy)(miip)](PF6)2·2H2O (2) (bpy is 2,2'-bipyridine; iip is 2-(imidazo-4-yl)-1H-imidazo[4,5-f] [1,10] phenanthroline; miip is 2-(1-methylimidazo-2-yl)-1H-imidazo[4,5-f] [1, 10] phenanthroline), have been synthesized and fully characterized by CHN analysis, electrospray ionization and MALDI-TOF mass spectrometry, (1)H NMR, FT-IR (ATR), and UV-Vis spectrophotometer. Cytotoxicity, ability to inhibit DNA transcription and DNAse activity of the complexes were studied. The DNA-binding behaviors of both complexes have also been studied by spectroscopic methods, cyclic voltammetry and viscosity measurements. Both complexes showed cytotoxic properties and 2 was more cytotoxic than 1. DNA transcription was inhibited upon increasing concentrations of both complexes. The complex 2 was found to be a better inhibitor than 1. The same pattern can be seen in the DNAse profile of the complexes. In addition, 2 was found to promote cleavage of pBR322 DNA at a lower concentration than 1. The spectroscopic, electrochemical and viscometric results indicate that both complexes show some degree of binding to DNA in an intercalative mode, resulting in intrinsic binding constants K b = 3.55 ± 0.6 × 10(4) M(-1) and 7.01 ± 0.9 × 10(4) M(-1) for 1 and 2, respectively. The difference in the DNA-binding affinities of 1 and 2 may presumably be explained by the methylated imidazole nitrogen atom that makes the compound more hydrophobic and gives better intercalative binding ability to DNA's hydrophobic environment.
Asunto(s)
ADN/química , Compuestos de Platino/química , Células Cultivadas , Humanos , Ligandos , Espectroscopía de Protones por Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
PURPOSE: Hepatocellar carcinoma (HCC) remains a major health problem being the third leading cause of deaths due to cancer worldwide. Because HCC is known to be highly resistant to conventional systemic therapies, single-agent or combination of systemic therapies have been investigated. Today, sorafenib, a multikinase inhibitor, is the only approved systemic agent for the first line treatment of advanced HCC. In this study, we aimed to investigate the influence of different concentrations of cisplatin, doxorubicin, pegylated doxorubicin (PLD), oxaliplatin and gemcitabine by applying these agents either single or in combinations on mahlavu cell line. METHODS: HCC mahlavu cell line was used for the experiments. Cell death was measured by flow cytometry at 48 hrs after incubation with various concentrations (0.1 µg/ml, 1.0 µg/ml and 10 µg/ml) of the drugs. RESULTS: Cell death due to gemcitabine was found to be significantly higher than cell deaths caused by the other single agents including cisplatin, oxaliplatin, doxorubicin and PLD (p<0.001, p<0.001, p<0.001 and p=0.0049, respectively). There was no significant difference between gemcitabine and both the gemcitabine combination with doxorubicin and PLD (p=0.992 and p=0.441, respectively). CONCLUSION: This is a preliminary analysis evaluating the effect of the conventional chemotherapeutic agents on mahlavu cell line in vitro. The findings of this study suggest that gemcitabine-based therapies keep on being the prefered therapeutic approach for the treatment of HCC.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Cisplatino/farmacología , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Doxorrubicina/farmacología , Humanos , Neoplasias Hepáticas/patología , Compuestos Organoplatinos/farmacología , Oxaliplatino , GemcitabinaRESUMEN
OBJECTIVES: The circumventricular organs (CVOs) are essential for most autonomic and endocrine functions. Trauma and bleeding can affect their function. The aim of this study was to investigate apoptosis and necrosis in CVOs in the early period after experimental subarachnoid hemorrhage (SAH) in rats, using annexin V affinity and caspase 3 immunostaining. METHODS: Three experimental groups were used: Days 1 and 2 after SAH, and a control group, seven Wistar albino rats each. Subarachnoid hemorrhage was accomplished by transclival basilar artery puncture. Rats were perfused with 0.9% NaCl and 0·1M phosphate buffer pH 7.4 until heart stoppage. Apoptosis and necrosis in CVOs were measured by flow cytometry with annexin V staining, and by caspase 3 immunostaining. RESULTS: Apoptosis in the organum vasculosum lamina terminalis (OVLT), median eminence (ME), and area postrema (AP) was significantly higher in the Day 1 group than in the control group. Apoptosis in the subfornicial organ (SFO), OVLT, ME, and AP was significantly higher in the Day 2 group than in the control group. There were significant differences between the Day 1 and Day 2 groups, except for AP. Necrosis in SFO and OVLT was significantly higher in the Day 2 group than in the Day 1 or control groups, whereas necrosis in the ME and AP did not differ between the three groups. Caspase 3-positive cell density was more intense in the Day 2 group than in the Day 1 and control groups. DISCUSSION: Prevention of apoptosis may potentially improve impaired functions of CVOs after SAH.