The organometallic AuI bis‐N‐heterocyclic carbene complex [Au(9‐methylcaffeine‐8‐ylidene)2]+ (AuTMX2) was previously shown to selectively and potently stabilise telomeric DNA G‐quadruplex (G4) structures. This study sheds light on the molecular reactivity and mode of action of AuTMX2 in the cellular context using mass spectrometry‐based methods, including shotgun proteomics in A2780 ovarian cancer cells. In contrast to other metal‐based anticancer agents, this organogold compound is less prone to form coordinative bonds with biological nucleophiles and is expected to exert its drug effects mainly by non‐covalent interactions. Global protein expression changes of treated cancer cells revealed a multimodal mode of action of AuTMX2 by alterations in the nucleolus, telomeres, actin stress‐fibres and stress‐responses, which were further supported by pharmacological assays, fluorescence microscopy and cellular accumulation experiments. Proteomic data are available via ProteomeXchange with identifier PXD020560.
The paper presents a highly selective analytical method for the determination of traces of bisphenol A (BPA) in wine and the results of a survey 59 wine samples sourced from vats (steel, wood and plastic), glass bottles and Tetra briks. The procedure consists of sample clean-up by sol-gel immunoaffinity chromatography followed by determination of BPA by high-performance liquid chromatography and fluorescence detection. The method has a limit of detection (LOD) (S/N = 3) of 0.1 ng ml−1 and a limit of quantitation (LOQ) (S/N = 6) of 0.2 ng ml−1. In 13 of 59 wine samples, the BPA concentration was below the LOQ. The mean and median for all wine samples with BPA concentrations above the LOQ were 0.58 and 0.40 ng ml−1, respectively. These values — the first set of data on BPA in wine — are far lower than previously published BPA levels derived from migration experiments using wine simulants. Experiments carried out by submerging plastic stoppers in ethanol–water (11 : 89, v/v) up to 11 weeks indicated that detectable amounts of BPA can be leached from some stoppers.
ATP-binding cassette (ABC) transporters play a crucial role in multidrug resistance (MDR) of cancers. They function as efflux pumps, resulting in limited effectiveness or even failure of therapy. Increasing evidence suggests that ABC transporters are also involved in tumor initiation, progression, and metastasis. Tumors frequently show multiple genetic and epigenetic abnormalities, including changes in histone modification and DNA methylation. Alterations in the DNA methylation status of ABC transporters have been reported for a variety of cancer types. In this review, we outline the current knowledge of DNA methylation of ABC transporters in cancer. We give a brief introduction to structure, function, and gene regulation of ABC transporters that have already been investigated for their DNA methylation status in cancer. After giving an overview of the applied methodologies and the CpGs analyzed, we summarize and discuss the findings on aberrant DNA methylation of ABC transporters by cancer types. We conclude our review with the discussion of the potential to target aberrant DNA methylation of ABC transporters for cancer therapy.