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Globally, cancer is a serious health problem. It is unfortunate that current anti-cancer strategies are insufficiently specific and damage the normal tissues. There's urgent need for development of new anti-cancer strategies. More recently, increasing attention has been paid to the new application of ferroptosis and nano materials in cancer research. Ferroptosis, a condition characterized by excessive reactive oxygen species-induced lipid peroxidation, as a new programmed cell death mode, exists in the process of a number of diseases, including cancers, neurodegenerative disease, cerebral hemorrhage, liver disease, and renal failure. There is growing evidence that inducing ferroptosis has proven to be an effective strategy against a variety of chemo-resistant cancer cells. Nano-drug delivery system based on nanotechnology provides a highly promising platform with the benefits of precise control of drug release and reduced toxicity and side effects. This paper reviews the latest advances of combination therapy strategies based on biomedical nanotechnology induced ferroptosis for cancer therapeutics. Given the new chances and challenges in this emerging area, we need more attention to the combination of nanotechnology and ferroptosis in the treatment of cancer in the future. [Display omitted] • Current anti-cancer strategies are lack of specificity and damage normal tissues. • Ferroptosis is an effective strategy against chemo-resistant cancer cells. • Nanotechnology provides of precise control of drug release and reduced toxicity. • Combination therapy based on ferroptosis-induced nano-DDS brings enhanced antitumor effect and has satisfactory safety. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the apoptotic effect of a proteasome inhibitor MG-132 on Tca-8113, a cell line of human tongue squamous cell carcinoma. Tca-8113 cells were treated with 10, 20, and 30μM of MG-132, or 5μM thapsigargin. Apoptosis rate was determined with annexin V/propidium iodide double staining. Expression of E3ubiquitin-protein ligase was determined by ELISA, and Grp78 and caspase-12 mRNA, and Grp78 and caspase-12 protein was assessed by RT-PCR and Western blot, respectively. Apoptosis was observed 18h after MG-132 treatment. The apoptotic rate in the 10, 20, and 30μM MG-132 group was 13.5, 19.6 and 34.7%, respectively, which was higher than in the thapsigargin (8.5%, P <0.01) or control group (0.5%, P <0.01). The expression of E3 ubiquitin-protein ligase in the 10, 20, and 30μM MG-132 group was 28.75±2.28, 18.16±0.65, 8.85±0.72, respectively, which was lower than in the thapsigargin (38.96±0.33, P <0.05 or 0.01) or control (40.88±4.52, P <0.05 or 0.01) group. The levels of Grp78 and capase-12 mRNA, Grp78 and caspase-12 protein in the MG-132 groups were higher than in the control group (P <0.01). In conclusion, MG-132 induces apoptosis in Tca-8113 cells in a concentration-dependent manner. The MG-132-induced apoptosis may involve downregulation of E3 ubiquitin ligase, and upregulation of Grp78 and caspase-12. [Copyright &y& Elsevier]

Background Nitric oxide (NO) is generated in endothelial cells by endothelial nitric oxide synthase (eNOS). Caveolin-1 (Cav1) inhibits eNOS function and NO production. Modifying Cav1 scaffold domain, in particular Phenylalanine at position 92 (F92) is critical for the inhibitory actions of Cav1 toward eNOS. The aims of this study were to investigate the effect of enhanced NO production in term of in vitro angiogenesis on rat bone marrow derived mesenchymal stem cells (BMSCs) transduced with a novel bicistronic lentiviral vector co-expressing eNOS and mutant Cav1 (F92A). Methods A bicistronic eNOS/F92-Cav1 lentiviral vector was constructed, and used to transduce rat BMSCs. The expression of eNOS and VEGF protein were confirmed by western-blot. NO production was detected by the greiss assay and in vitro angiogenesis was assessed by matrigel assisted capillary tube formation. The cell viability was evaluated using a Cell Counting Kit (CCK)-8. Results The bicistronic eNOS/F92A-Cav1 lentiviral vector increased eNOS and VEGF protein expression, NO production compared to controls. In vitro capillary formation was increased in eNOS-F92A transduced cells and cell viability was not affected by transduction. Conclusion Transduction of rat BMSCs with an eNOS-F92A-Cav1 lentiviral vector can increase NO production by enhancing eNOS protein expression. The increased NO production did not reduce cell viability. This study demonstrates that genetic modification of BMSCs to enhance NO producton could be applied in stem cell based therapeutic approaches to treat diseases such as pulmonary arterial hypertension (PAH) which is characterized by decreased endothelial NO release. [ABSTRACT FROM AUTHOR]

Abstract: This study was designed to investigate the function of 17β-estradiol (17β-E2) against oxidative stress on the cell death of mice bone marrow mesenchymal stem cells (BMSCs) induced by hydrogen peroxide (H2O2). BMSCs were treated with 17β-E2 for 24h and then treated with 100μM H2O2 for 1h. Cell viability, apoptosis, caspase-9 mRNA, JNKs (Jun N-terminal kinases) and c-Jun protein expression in BMSCs were evaluated. Cell apoptosis of BMSCs were increased in a dose-dependent manner after treated with H2O2 compared to control group. But pretreatment with 17β-E2 can inhibit apoptosis of BMSCs, preserve the mitochondrial transmembrane potential, decrease caspase-9 mRNA, JNK1/2 and c-Jun protein expression. In conclusion, 17β-E2 exerts antiapoptotic effects in BMSCs which related to the mitochondria death pathway and JNKs pathway. The study revealed that 17β-E2 can reduce the donor stem cells damage. [Copyright &y& Elsevier]

Ovarian cancer is the most lethal gynecologic malignancy and the fifth most lethal cancer type overall in women. Ovarian cancer often presents genome instability, with almost half of the ovarian cancers harbor defects in one or more of the six DNA repair pathways, most of them in homologous recombination (HR). Targeting DNA repair genes has becoming a unique strategy to combat HR-deficient cancers in recent years. The multi-functional enzyme Poly ADP ribose polymerase (PARP) plays an impart role in DNA damage repair and genome stability. PARP inhibitors inhibit DNA repair pathways and cause apoptosis of cancer cells, especially in homologous recombination (HR)-deficient cells. PARP inhibitors (PARPi) have drawn increasing amount of attention due to their remarkable efficacy and low toxicity in treating HR-deficient ovarian cancers (i.e. BRCA1/2 mutated). To date, three PARP inhibitor drugs have been approved for treating ovarian cancer by FDA in United States, namely Olaparib, Rucaparib, and Niraparib. In this review, we summarized the current research progress of PARPi from basic science to clinical studies. We discussed the mechanism of action of PARP inhibitors and the exciting results from the clinical studies of the FDA-approved PARP inhibitors. We also highlighted the current research progress on PARP inhibitor resistance, which has become a challenge in clinics. [ABSTRACT FROM AUTHOR]

Background Cell based therapy has been heralded as a novel, promising therapeutic strategy for cardiovascular diseases including pulmonary arterial hypertension (PAH). However, the low survival rate after transplantation due to cell death via anoikis is a major obstacle in stem cell therapy. Cells adhesion via Integrin alpha5beta1 (ITGA5B1) has a tendency to exert higher maximum forces. The present study aimed to evaluate the potential protective effect of ITGA5B1 on rat bone marrow mesenchymal stem cells (rBMSCs) from anoikis. Methods Mononuclear cells were isolated by density gradient centrifugation with Ficoll, and rBMSCs cell surface markers were evaluated by flow cytometry. Osteogenic and adipocyte differentiation was determined by Alizarin Red S and Oil Red O staining respectively. The expression of Integrin A5 (ITGA5), Integrin B1 (ITGB1), eNOS and actived-caspase-3 mRNA or protein was confirmed by qPCR and western-blot. Cell adhesion, cell viability, anoikis and the migration of rBMSCs were also evaluated. Nitric oxide (NO) production was detected by the greiss assay. Results Co-infected with Integrin A5 and B1 lentivirus to rBMSCs increased ITGA5 and ITGB1 mRNA and protein expression. ITGA5B1 enhanced the cell adhesion, cell viability, cell migration and NO production but reduced the cell anoikis in rBMSCs/ITGA5B1 groups. Conclusion Transduction of rat rBMSCs with ITGA5B1 lentivirus could prevent cell anoikis and increase NO production. [ABSTRACT FROM AUTHOR]

There is growing evidence that epithelial mesenchymal-transition (EMT) plays significant roles in terms of tumor metastasis. There are a lot of cytokines inducing EMT of tumor cells, EGF is one of the important cytokines.Ezrin is a connexin between the cytoskeleton and the cell membrane, which is closely related to the morphological movement and metastasis of tumor cells.EGF can activate Ezrin and affects cell motility. In recent years, many studies have shown that NF-kB acts as an important transcription factor, involving in the process of EMT. However, does Ezrin participate in the regulation of EGF-induced EMT through the NF-kB pathway? This question needs us to discuss.In the present study, we found that EGF could induce colorectal cancer cells to develop EMT,enhance their ability to invade and migrate and promotes phosphorylation of Ezrin Tyr353.On the other hand, inhibition of Ezrin could reverse EGF-induced EMT and inhibit NF-kB P65 translocating into the nucleus. Finally, knockout of Ezrin inhibited EGF-induced lung metastasis of colorectal cancer xenografts and abnormal activation of Ezrin and NF-kB were related with colorectal cancer metastasis and poor prognosis. Our present results suggest that Ezrin/NF-kB pathway may provide experimental evidence for new targeted drugs for colorectal cancer metastasis. [ABSTRACT FROM AUTHOR]

Exposure of Tca-8113 cells to proteasome inhibitor carbobenzoxy-Leu-Leu-leucinal (MG-132) causing apoptosis is associated with endoplasmic reticulum (ER) stress. X-box-binding protein-1 (XBP1) is an important regulator of a subset of genes active during ER stress, which is related to cell survival and is required for tumor growth. The present study is to evaluate the effect of MG-132 on ROS production, XBP1 gene expression, tumor necrosis factor receptor-associated factor 2 (TRAF2), ASK1 and c -jun protein expression in tongue squamous cell carcinoma cell line Tca-8113 cells. ROS production was measured by reactive oxygen species assay. X-box binding protein-1 (XBP1) mRNA was analyzed by real-time–PCR, TRAF2, ASK1 and c -jun protein were investigated by western blot and immunocytochemistry respectively. The result indicated that ROS production, TRAF2, ASK1 and c -jun were elevated in MG-132 treated cells. Giving ROS scavenger N -acetyl- L -cysteine (NAC) largely prevented the effects of MG-132. Furthermore, treating with MG-132 lead to decreased XBP1 mRNA expression but could not completely block the expression of XBP1. Taken together, these findings provide the evidence that MG-132 induced ER stress lead to Tca-8113 cells apoptosis through ROS generation and TRAF2-ASK1-JNK signal pathway activation. [ABSTRACT FROM AUTHOR]

Abstract: This study was aimed to investigate the effect of down-regulating the CXC chemokine receptor-4 (CXCR4) expression on cell proliferation, invasion and migration of human ovarian cancer cell line SW626. The CXCR4 specific short hairpin RNA (shRNA) plasmid vector was constructed and then transfected into the SW626 cells. The expression of CXCR4 mRNA and protein was detected by real-time RT-PCR and western blot respectively. Cell proliferation was detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell invasion and migration was assayed in Biocoat Matrigel invasion chambers. The expression level of CXCR4 in SW626 cell transfected with CXCR4-siRNA was inhibited, leading to significant decrease in SW626 cell proliferation, invasion and migration. We conclude that CXCR4 is essential for tumor cell proliferation and invasion. The CXCR4 molecule is a potential therapeutic target to control ovarian cancer cell growth or metastasis. [Copyright &y& Elsevier]