The biosafety issue of nanoscale materials is getting more and more attention with their increasing manufacture and application. In the research of cellular effects and underlying mechanisms related to toxicity of nanomaterials, most emphasis were placed on processes such as apoptosis, metabolic inhibition and oxidative stress. Recent evidence suggests that autophagy is part of the biological effects by nanomaterials and various kinds of nanomaterials are capable of disturbing the autophagic process. This review will highlight the importance of autophagy as an emerging mechanism of nanomaterial toxicity and the implication in the therapy of autophagy-related diseases. We summarize current research status of interaction between nanomaterials and autophagic pathways. It is of note that nanomaterials can either induce or block autophagy, which result in similar phenotype but completely different biological consequence. It is therefore important to perform comprehensive analysis of the whole autophagic flux in the future research. Nanomaterials refer to materials with the size range between 1 and 100 nanometers in one or more dimensions [1]. Due to their superior physicochemical properties, such as ultra small size, increased ratio of surface area to volume, multiple options for modification and relatively good biocompatibilities, application of nanomaterials in research as well as in industry becomes more and more common. It is predicted that the total amount of nanomaterials' production will increase up to 58000 tons by 2020. Particularly, the utilization of nanomaterials in biomedical research as biosensors, drug-carriers, or imaging agents was extensively studied [2][3][4]. Large scaled preparation and application of nanomaterials increase their possibilities to be exposed to human beings or enter the environment [5][6][7]. Therefore the impact of nanomaterials on environment and human health has attracted high attention. Related studies were carried out on the biological effect of various kinds of nanomaterials both in vitro and in vivo [8]. To date, reported physiological changes of a cell or an organism that exposed to nanomaterials include: reactive oxygen species (ROS)-related pathological responses (such as damaged membrane, mitochondrial damage and necrosis), apoptosis, inflammation and altered differentiation patterns, etc [9][10][11][12]. Recently, autophagy as an essential cellular process and a novel biological effect of nanomaterials on eukaryotes, has received much attention. Many nanomaterials were reported to be able to change the basal level of autophagy [13,14]. Autophagy can crosstalk with other cellular process, such as apoptosis and necrosis, and therefore is an important part of the cellular effect of nanomaterials [15,16]. Moreover, nanomaterials-induced autophagy showed potential for the treatment of certain diseases including neurodegenerative diseases and cancer [13,17]. Hence, in this review we summarize the current research on the effect of various kinds of nanomaterials on autophagy. ...
Blockage of autophagic flux by nanodiamonds induces apoptosis in hypoxic tumor cells with minimal toxicity to normal tissues and enhances the effects of anti-angiogenic therapy.
Benzoxazole derivative K313 has previously been reported to possess anti-inflammatory effects in lipopolysaccharide-induced RAW264.7 macrophages. To date, there have been no related reports on the anticancer effects of K313. In this study, we found that K313 reduced the viability of human B-cell leukemia (Nalm-6) and lymphoma (Daudi) cells in a dose-dependent manner without affecting healthy peripheral blood mononuclear cells (PBMCs) and induced moderate cell cycle arrest at the G0/G1 phase. Meanwhile, K313 mediated cell apoptosis, which was accompanied by the activation of caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP). Furthermore, cells treated with K313 showed a significant decrease in mitochondrial membrane potential (MMP), which may have been caused by the caspase-8-mediated cleavage of Bid, as detected by Western blot analysis. We also found that K313 led to the downregulation of p-p70S6K protein, which plays an important role in cell survival and cell cycle progression. In addition, treatment of these cells with K313 blocked autophagic flux, as reflected in the accumulation of LC3-II and p62 protein levels in a dose- and time-dependent manner. In conclusion, K313 decreases cell viability without affecting normal healthy PBMCs, induces cell cycle arrest and apoptosis, reduces p-p70S6K protein levels, and mediates strong autophagy inhibition. Therefore, K313 and its derivatives could be developed as potential anticancer drugs or autophagy blockers in the future.
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