Background Tumor progression and tumor response to anticancer therapies may be affected by activation of oncogenic pathways such as the antioxidant one induced by NRF2 (nuclear factor erythroid 2-related factor 2) transcription factor and the pathways modified by deregulation of oncosuppressor p53. Often, oncogenic pathways may crosstalk between them increasing tumor progression and resistance to anticancer therapies. Therefore, understanding that interplay is critical to improve cancer cell response to therapies. In this study we aimed at evaluating NRF2 and p53 in several cancer cell lines carrying different endogenous p53 status, using a novel curcumin compound since curcumin has been shown to target both NRF2 and p53 and have anti-tumor activity. Methods We performed biochemical and molecular studies by using pharmacologic of genetic inhibition of NRF2 to evaluate the effect of curcumin compound in cancer cell lines of different tumor types bearing wild-type (wt) p53, mutant (mut) p53 or p53 null status. Results We found that the curcumin compound induced a certain degree of cell death in all tested cancer cell lines, independently of the p53 status. At molecular level, the curcumin compound induced NRF2 activation, mutp53 degradation and/or wtp53 activation. Pharmacologic or genetic NRF2 inhibition further increased the curcumin-induced cell death in both mutp53- and wtp53-carrying cancer cell lines while it did not increase cell death in p53 null cells, suggesting a cytoprotective role for NRF2 and a critical role for functional p53 to achieve an efficient cancer cell response to therapy. Conclusions These findings underline the prosurvival role of curcumin-induced NRF2 expression in cancer cells even when cells underwent mutp53 downregulation and/or wtp53 activation. Thus, NRF2 inhibition increased cell demise particularly in cancer cells carrying p53 either wild-type or mutant suggesting that p53 is crucial for efficient cancer cell death. These results may represent a paradigm for better understanding the cancer cell response to therapies in order to design more efficient combined anticancer therapies targeting both NRF2 and p53.
Over the last few years, the risk to human health related to asbestos fiber exposure has been widely demonstrated by many studies. Serpentinites are the main rocks associated with naturally occurring asbestos (NOA). In order to investigate the presence of NOA, a mineralogical study was conducted on eleven serpentinite samples collected nearby the village of Episcopia (Lucania, Southern Italy). Various analytical techniques such as X-ray powder diffraction (XRPD), scanning electron microscopy combined with energy dispersive spectrometry (SEM-EDS) and derivative thermogravimetry (DTG) were used to determine the occurrence of asbestos minerals and to make morphological observations. Results pointed out that all of the samples contain asbestos minerals (e.g., tremolite, actinolite and chrysotile). Moreover, it was observed that both natural processes and human activity may disturb NOA-bearing outcrops and provoke the formation of potentially inhalable airborne dust causing the release of asbestos fibers into the environment, thereby increasing the risk to human health. For this reason, our study aims to highlight the requirement of a natural asbestos survey and periodic update in the area.
The hyperactivation of nuclear factor erythroid 2 p45-related factor 2 (NRF2), frequently found in many tumor types, can be responsible for cancer resistance to therapies and poor patient prognosis. Curcumin has been shown to activate NRF2 that has cytotprotective or protumorigenic roles according to tumor stage. The present study aimed at investigating whether the zinc–curcumin Zn(II)–curc compound, which we previously showed to display anticancer effects through multiple mechanisms, could induce NRF2 activation and to explore the underlying molecular mechanisms. Biochemical studies showed that Zn(II)–curc treatment increased the NRF2 protein levels along with its targets, heme oxygenase-1 (HO-1) and p62/SQSTM1, while markedly reduced the levels of Keap1 (Kelch-like ECH-associated protein 1), the NRF2 inhibitor, in the cancer cell lines analyzed. The silencing of either NRF2 or p62/SQSTM1 with specific siRNA demonstrated the crosstalk between the two molecules and that the knockdown of either molecule increased the cancer cell sensitivity to Zn(II)–curc-induced cell death. This suggests that the crosstalk between p62/SQSTM1 and NRF2 could be therapeutically exploited to increase cancer patient response to therapies.
Ag(I)‐containing ethylcellulose (EC) films suitable as antbacterial packaging materials have been prepared and fully characterized. Different preparation methods, including the use of green casting solvents, are proposed. The Ag(I) acylpyrazolonato complexes, [Ag(Qpy,CF3)(L)], L=benzylimidazole (Bzim) and L=ethylimidazole (EtimH), used as active additives, display different modes of interactions with EC, depending on their structural features. A thorough investigation of the EC liquid‐crystalline lyotropic phase and its changes with the introduction of silver additives, has been conducted, revealing either the inclusion of complex molecules into the inner structure of the EC matrix or their dispersion on its surface. Moreover, the bactericidal activity of the prepared Ag(I) films seems to be related to the interaction between silver additives and the polymeric EC matrix. Indeed, the EC‐2b films show a particularly good performance even with a low silver content, with a relative bacterial killing of about 100 %. Tests for Ag(I) migration have been performed by using three food stimulants under two assay conditions. Low values of silver release are recorded, particularly at low concentration of silver content, in the case of all new prepared Ag(I) films.
In this paper, we report the quantification of potentially toxic elements (PTEs) hosted into two tremolite asbestos from Episcopia and San Severino Lucano villages (Basilicata region, Southern Italy). Micro X-ray fluorescence and Inductively Coupled Plasma spectroscopy with Optical Emission Spectrometry techniques were used to quantify the concentration of major, minor (Si, Mg, Ca, Al, Fe, Mn) and trace elements (As, Ba, Cd, Co, Cr, Cu, Li, Mo, Ni, Pb, Sb, Sn Sr, Ti, Te, V, W, Zn, Zr), with the aim of providing available data useful for the determination of the asbestos fibers toxicity. Results show that in the two studied samples there exist high concentrations of Fe, Mn, Cr and Ni which could lead to the high toxicity of the mineral fibers. By considering the pseudo-total PTEs amounts in each tremolite asbestos, it is possible to affirm that one of the samples is more enriched in toxic elements than the other one (3572 ppm versus 1384 ppm). These PTEs can represent a source of risk to human health since they may be transported away from the geological outcrops, through asbestos in the air, water and soils and thus encountering the human body.
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