A variety of metal-binding compounds have been found to exert anti-cancer activity. We postulated that N-acetylcysteine (NAC), which is a membrane-permeable metal-binding compound, might have anti-cancer activity in the presence of metals. We found that NAC/Cu(II) significantly alters growth and induces apoptosis in human cancer lines, yet NAC/Zn(II) and NAC/Fe(III) do not. We further confirmed that this cytotoxicity of NAC/Cu(II) is attributed to reactive oxygen species (ROS). These findings indicate that the combination of Cu(II) and thiols generates cytotoxic ROS that induce apoptosis in cancer cells. They also indicate a fourth class of anti-neoplastic metal-binding compounds, the “ROS generator”.
Zinc at cytotoxic concentrations has been shown to regulate gene transcription in cancer cells, though zinc′s involvement in posttranscriptional regulation is less characterized. In this study, we investigated the involvement of cytotoxic zinc in the posttranscriptional steps of gene expression. Clioquinol, a well-established zinc ionophore, was used to raise intracellular zinc to reported cytotoxic levels. The MCF-7 human cancer cell line was applied as a cell model system. Several parameters were used as indictors of posttranscriptional regulation, including p-body formation, microRNA profiling, expression level of proteins known to regulate mRNA degradation, microRNA processing, and protein translation. p-body formation was observed in MCF-7 cells using several molecules known as p-body components. Clioquinol plus zinc enhanced p-body assembly in MCF-7 cells. This enhancement was zinc-specific and could be blocked by a high affinity zinc chelator. The enhancement does not seem to be due to a stress response, as paclitaxel, a commonly used chemotherapeutic, did not cause enhanced p-body formation at a highly cytotoxic concentration. microRNA profiling indicated that clioquinol plus zinc globally down-regulates microRNA expression in this model system, which is associated with the reduced expression of Dicer, an enzyme key to microRNA maturation, and Ago2, a protein essential for microRNA stability. This study demonstrates that ionophoric zinc can induce cytotoxicity in cancer cells by globally regulating posttranscriptional events.
= 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-diethylamino-1,3,5-triazine) and [VO(C 12 H 8 N 2 )-(C 9 H 7 NO 3 )]ÁCH 3 OHÁ0.5H 2 O (3) were synthesized and characterized by elemental analysis, IR spectra, UV-Vis spectroscopy and single-crystal X-ray diffraction. In addition, the catalytic performances of complexes 1-3 and their starting materials (VO(acac) 2 and VOSO 4 ) were studied by the reaction of cyclohexane (Cy) oxidation.It is found that complex 1 exhibited the highest catalytic activity (TON (cyclohexanol) = 220, TON (cyclohexanone) = 346, Conv. = 97.9%) with H 2 O 2 as an oxidant and HNO 3 as an additive at 24 h, 40 1C, indicating that it is a potential candidate catalyst to oxidize the Cy to cyclohexanol (CyOH) and cyclohexanone (CyO) under mild conditions.
Two vanadium(iii) complexes were synthesized. Hydrogen peroxide was detected by a colorimetric method based on catalytic bromination reactions with the complexes as catalysts.
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