The Reduced Graphene Oxide (rGO) Induces Apoptosis, Autophagy and Cell Cycle Arrest in Breast Cancer Cells

Reduced graphene oxide (rGO) has already been reported as a potential cytostatic agent in various cancers. However, the mechanisms underlying rGO’s cytotoxicity are still insufficiently understood. Thus, the aim of the study was to investigate the molecular and cellular effects of rGO in breast cancer. Given this, two cell lines, MDA-MB-231 and ZR-75-1, were analyzed using MTT test, flow cytometry and Western blot assay. Incubation with rGO resulted in a multitude of effects, including the stimulation of autophagy, cell cycle arrest and, finally, the apoptotic death of cancer cells. Notably, rGO had minimal effect on normal human fibroblasts. Apoptosis in cancer cells was accompanied by decreased mitochondrial membrane potential, the deregulated expression of mitochondrial proteins and the activation of caspase 9 and caspase 3, suggesting that rGO predominantly induced apoptosis via intrinsic pathway. The analysis of LC3 protein expression revealed that rGO also caused autophagy in breast cancer cells. Moreover, rGO treatment resulted in cell cycle arrest, which was accompanied by deregulated p21 expression. Altogether, rGO seems to have multidirectional cytostatic and cytotoxic effects in breast cancer cells, making it a promising agent worthy of further investigation

Senescence of Tumor Cells in Anticancer Therapy—Beneficial and Detrimental Effects

Cellular senescence process results in stable cell cycle arrest, which prevents cell proliferation. It can be induced by a variety of stimuli including metabolic stress, DNA damage, telomeres shortening, and oncogenes activation. Senescence is generally considered as a process of tumor suppression, both by preventing cancer cells proliferation and inhibiting cancer progression. It can also be a key effector mechanism for many types of anticancer therapies such as chemotherapy and radiotherapy, both directly and through bioactive molecules released by senescent cells that can stimulate an immune response. Senescence is characterized by a senescence-associated secretory phenotype (SASP) that can have both beneficial and detrimental impact on cancer progression. Despite the negatives, attempts are still being made to use senescence to fight cancer, especially when it comes to senolytics. There is a possibility that a combination of prosenescence therapy—which targets tumor cells and causes their senescence—with senotherapy—which targets senescent cells, can be promising in cancer treatment. This review provides information on cellular senescence, its connection with carcinogenesis and therapeutic possibilities linked to this process

Low-glucose medium induces ORP150 expression and exerts inhibitory effect on apoptosis and senescence of human breast

MCF7 cell

Hypoxia Enhances the Senescence Effect of Bortezomib—The Proteasome Inhibitor—On Human Skin Fibroblasts

The 26S proteasome inhibitor, bortezomib, selectively induces apoptosis in some cancer cells. However, the nature of its selectivity remains unknown. The study presented here provides novel information on cellular effects of bortezomib in normal fibroblasts. We have found that in normoxic conditions the percent of apoptotic cells did not change significantly, independently on incubation time and examined concentration of bortezomib (25 nmol/L or 50 nmol/L). In hypoxic conditions we did not observe any effect of bortezomib on apoptosis of fibroblasts incubated for 24 h and 48 h in comparison to control. Only in the case of fibroblasts incubated for 12 hours in hypoxia significant increase in apoptosis, dependent on concentration of bortezomib, was observed. Our study has shown that bortezomib causes a time-dependent increase in senescence of normal fibroblasts, especially of these incubated in hypoxic conditions. Moreover, we demonstrated that oxygen regulated protein 150 (ORP150) expression was induced in fibroblasts in hypoxia conditions only, suggesting that this protein may play an important role in the cytoprotective response to environmental stress

The Preliminary Study on the Proapoptotic Effect of Reduced Graphene Oxide in Breast Cancer Cell Lines

Breast cancer is the most common cancer diagnosed in women, however traditional therapies have several side effects. This has led to an urgent need to explore novel drug approaches to treatment strategies such as graphene-based nanomaterials such as reduced graphene oxide (rGO). It was noticed as a potential drug due to its target selectivity, easy functionalisation, chemisensitisation, and high drug-loading capacity. rGO is widely used in many fields, including biological and biomedical, due to its unique physicochemical properties. However, the possible mechanisms of rGO toxicity remain unclear. In this paper, we present findings on the cytotoxic and antiproliferative effects of rGO and its ability to induce oxidative stress and apoptosis of breast cancer cell lines. We indicate that rGO induced time- and dose-dependent cytotoxicity in MDA-MB-231 and ZR-75-1 cell lines, but not in T-47D, MCF-7, Hs 578T cell lines. In rGO-treated MDA-MB-231 and ZR-75-1 cell lines, we noticed increased induction of apoptosis and necrosis. In addition, rGO has been found to cause oxidative stress, reduce proliferation, and induce structural changes in breast cancer cells. Taken together, these studies provide new insight into the mechanism of oxidative stress and apoptosis in breast cancer cells

The Effect of Silica Nanoparticles (SiNPs) on Cytotoxicity, Induction of Oxidative Stress and Apoptosis in Breast Cancer Cell Lines

Breast cancer is one of the most common cancers in women. Silica nanoparticles (SiNPs) belong to the group of often-used nanoparticles in biomedical applications. The mechanisms of the cytotoxicity, apoptosis, and oxidative stress induced by the 5–15 nm SiNPs still remain unclear. The aim of the study was to evaluate the anti-cancer effect and mechanism of action of SiNPs in breast cancer cell lines. The breast cancer MDA-MB-231 and ZR-75-1 cell lines were analyzed using MTT assay, flow cytometry, and spectrophotometric methods. In this paper, we presented findings about the cytotoxicity, apoptosis, and oxidative stress in both breast cancer cell lines. We indicated that 5–15 nm SiNPs induced dose-dependent cytotoxicity in MDA-MB-231 and ZR-75-1 cells. Moreover, we demonstrated that the process of apoptosis in the studied cell lines was associated with a decrease in the mitochondrial membrane potential (ΔΨm) and an increase in the activity of caspase-9 and caspase-3. Based on the obtained results, 5–15 nm SiNPs are able to induce the mitochondrial apoptosis pathway. Analyzed nanoparticles have also been found to cause an increase in selected oxidative stress parameters in both breast cancer cell lines. The presented study provides an explanation of the possible mechanisms of 5–15 nm SiNPs action in breast cancer cells

Reduced expression of E-cadherin and increased sialylation level in clear cell renal cell carcinoma

Cancer cells are characterized by an aberrant increase in protein N-glycosylation and by disruption of E-cadherin-mediated adherens junctions. However, the relationship between alterations in N-glycosylation process and loss of E-cadherin adhesion in cancer remains unclear. The mechanisms of altered expression of adhesive glycoproteins in cancer cells have not been fully elucidated. Thus, the aim of this study was to examine the expression of E-cadherin and sialyl Lewisa/x, NeuAcα2-3Gal, NeuAcα2-6Gal/GalNAc structures in the normal renal tissue and intermediate and cancerous tissues from patients with clear cell RCC. Moreover, we attempted to correlate the E-cadherin expression with some specific sugar residues of renal cancer tissue glycoproteins. The expression of E-cadherin was analysed using ELISA test and immunoblotting. Oligosaccharide structures and sialylation level were detected with ELISA test using specific biotinylated lectins or antibodies. A significant decrease of E-cadherin expression as well as a significant increase in sialylated oligosaccharides level in intermediate zone and renal cancer tissue in comparison to normal renal tissue are reported. Significant decrease in expression of cadherins and increase in sialylation of oligosaccharide structures in renal cancer tissue in comparison to normal renal tissue, and in renal cancer tissue in comparison to intermediate zone of renal tissue, are important for the future research concerning detection and quantification of cadherins and sialylated oligosaccharide structures in urine and cells of urinary sediment as possible non-invasive marker of early RCC

A Preliminary Study of the Effect of Quercetin on Cytotoxicity, Apoptosis, and Stress Responses in Glioblastoma Cell Lines

A growing body of evidence indicates that dietary polyphenols show protective effects against various cancers. However, little is known yet about their activity in brain tumors. Here we investigated the interaction of dietary flavonoid quercetin (QCT) with the human glioblastoma A172 and LBC3 cell lines. We demonstrated that QCT evoked cytotoxic effect in both tested cell lines. Microscopic observations, Annexin V-FITC/PI staining, and elevated expression and activity of caspase 3/7 showed that QCT caused predominantly apoptotic death of A172 cells. Further analyses confirmed enhanced ROS generation, deregulated expression of SOD1 and SOD2, depletion of ATP levels, and an overexpression of CHOP, suggesting the activation of oxidative stress and ER stress upon QCT exposure. Finally, elevated expression and activity of caspase 9, indicative of a mitochondrial pathway of apoptosis, was detected. Conversely, in LBC3 cells the pro-apoptotic effect was observed only after 24 h incubation with QCT, and a shift towards necrotic cell death was observed after 48 h of treatment. Altogether, our data indicate that exposure to QCT evoked cell death via activation of intrinsic pathway of apoptosis in A172 cells. These findings suggest that QCT is worth further investigation as a potential pharmacological agent in therapy of brain tumors