For many years, there has been uncertainty concerning the reason for Hsp70 translocation to the nucleus and nucleolus. Herein, we propose that Hsp70 translocates to the nucleus and nucleoli in order to participate in pathways related to the protection of the nucleoplasmic DNA or ribosomal DNA from single-strand breaks. The absence of Hsp70 in HeLa cells, via Hsp70 gene silencing (knockdown), indicated the essential role of Hsp70 in DNA integrity. Therefore, HeLa Hsp70 depleted cells were very sensitive in heat treatment and their DNA breaks were multiple compared to that of control HeLa cells. The molecular mechanism with which Hsp70 performs its role at the level of nucleus and nucleolus during stress was examined. Hsp70 co-localizes with PARP1 in the nucleus/nucleoli as was observed in confocal studies and binds to the BCRT domain of PARP1 as was revealed with protein-protein interaction assays. It was also found that Hsp70 binds simultaneously to XRCC1 and PARP-1,

Heat shock protein 70 (Hsp70; also known as HSP70A1A) is one of the most induced proteins in cancer cells; however, its role in cancer has not yet been fully elucidated. In the present study, we proposed a hypothetical model in which the silencing of Hsp70 enhanced the metastatic properties of the HeLa, A549 and MCF7 cancer cell lines. We consider that the inability of cells to form cadherin-catenin complexes in the absence of Hsp70 stimulates their detachment from neighboring cells, which is the first step of anoikis and metastasis. Under these conditions, an epithelial-to-mesenchymal transition (EMT) pathway is activated that causes cancer cells to acquire a mesenchymal phenotype, which is known to possess a higher ability for migration. Therefore, we herein provide evidence of the dual role of Hsp70 which, according to international literature, first establishes a cancerous environment and then, as suggested by our team, regulates the steps of the metastatic process, including EMT and migration. Finally, the trigger for the anti-metastatic properties that are acquired by cancer cells in the absence of Hsp70 appears to be the destruction of the Hsp70-dependent heterocomplexes of E-cadherin/catenins, which function like an anchor between neighboring cells.

In 40 healthy persons, 11 nondialyzed uremic patients and 27 dialyzed uremic patients, of whom 4 also had cancer, the selenium concentration in serum was determined. The mean serum selenium concentration in healthy persons was 13.6 ± 0.8 μg/dl, in nondialyzed patients 11.9 ± 1.9 μg/dl and in dialyzed uremic patients 11.3 ± 1.0 μg/dl. There was a significant statistical difference between healthy persons and uremic patients (p < 0.00l), but not between dialyzed and nondialyzed uremic patients. The subgroup of cancer patients on hemodialysis also had low serum selenium concentrations. The possible role of low selenium levels as one of the factors responsible for the increased incidence of malignancy in patients with chronic renal failure is supported by several facts such as: (a) low serum selenium levels detected in patients with malignant diseases; (b) the higher cancer incidence in inhabitants of low-selenium areas, and (c) the known ability of selenium to inhibit many types of experimental carcinogenesis.

Trace element selenium (Se) is regarded to be a breast cancer preventive factor involved in multiple protective pathways. In all, 80 women with breast cancer who underwent a radical mastectomy were enrolled in the study. Serum Se and carcinoembryonic antigen levels were measured using a fluorometric and IRMA assay, respectively. Se tissue concentration was determined by a tissue extracting fluorometric assay. For statistical analysis purposes t -test was used and P -values <0.001 were regarded as statistically significant. Serum Se was 42.5±7.5 μ g l −1 in breast cancer patients and 67.6±5.36 μ g l −1 in the age-matched control group of healthy individuals. Serum carcinoembryonic antigen in patients was 10±1.7 U ml −1 (normal <2.5 U ml −1 in nonsmokers/<3.5 U ml −1 in smokers). A statistically significant difference was found for both serum Se and CEA between two groups studied ( P <0.001). Neoplastic tissue Se concentration was 2660±210 mg g −1 tissue; its concentration in the adjacent non-neoplastic tissue was 680±110 mg g −1 tissue ( P <0.001). An inverse relationship between Se and CEA serum levels was found in the two groups studied ( r =−0.794). There was no correlation between serum/tissue Se concentration and stage of the disease. The decrease in serum Se concentration as well as its increased concentration in the neoplastic breast tissue is of great significance. These alterations may reflect part of the defence mechanisms against the carcinogenetic process.

The aim of this study was to investigate the potential protective effect of the Hsp70 protein in the cardiac dysfunction induced by doxorubicin (DOX) and the mechanisms of its action. For this purpose, we used both wild-type mice (F1/F1) and Hsp70-transgenic mice (Tg/Tg) overexpressing human HSP70. Both types were subjected to chronic DOX administration (3 mg/kg intraperitoneally every week for 10 weeks, with an interval from weeks 4 to 6). Primary cell cultures isolated from embryos of these mice were also studied. During DOX administration, the mortality rate as well as weight reduction were lower in Tg/Tg compared to F1/F1 mice (P < 0.05). In vivo cardiac function assessment by transthoracic echocardiography showed that the reduction in left ventricular systolic function observed after DOX administration was lower in Tg/Tg mice (P < 0.05). The study in primary embryonic cell lines showed that the apoptosis after incubation with DOX was reduced in cells overexpressing Hsp70 (Tg/Tg), while the apoptotic pathway that was activated by DOX administration involved activated protein factors such as p53, Bax, caspase-9, caspase-3, and PARP-1. In myocardial protein extracts from identical mice with DOX-induced heart failure, the particular activated apoptotic pathway was confirmed, while the presence of Hsp70 appeared to inhibit the apoptotic pathway upstream of the p53 activation. Our results, in this DOX-induced heart failure model, indicate that Hsp70 overexpression in Tg/Tg transgenic mice provides protection from myocardial damage via an Hsp70-block in p53 activation, thus reducing the subsequent apoptotic mechanism.