AREL1 resists the apoptosis induced by TGF-β by inhibiting SMAC in vascular endothelial cells

Abnormal apoptosis of vascular endothelial cells is an important feature of arteriosclerosis (AS). Here, we induced apoptosis in human umbilical vein endothelial cells (HUVECs) using transforming growth factor-β (TGF-β), and investigated the role of antiapoptotic E3 ubiquitin ligase (AREL1) in the apoptosis of vascular endothelial cells. We proved that AREL1 is downregulated in TGF-β treated HUVECs. The overexpression of AREL1 inhibits the activation of Caspase-3 and Caspase-9 and attenuates cell apoptosis induced by TGF-β. According to the result of coimmunoprecipitation, AREL1 interacts with the proapoptotic proteins the second mitochondria-derived activator of caspases (SMAC) in TGF-β treated HUVECs. In addition, miR-320b inhibits the expression of AREL1, and the overexpression of AREL1 attenuates the apoptosis induced by miR-320b mimics in HUVECs. In conclusion, AREL1 is downregulated by miR-320b. AREL1 overexpression inhibits TGF-β induced apoptosis through downregulating SMAC in vascular endothelial cells. Our study explores pathogenesis regulation mechanism and new biological therapeutic targets for vascular disease.     

Dieckol,a natural polyphenolic drug,inhibits the proliferation and migration of colon cancer cells by inhibiting PI3K,AKT, and mTOR phosphorylation

This study investigated that dieckol (DKL), a natural drug, inhibits colon cancer cell proliferation and migration by inhibiting phosphoinositide-3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) phosphorylation in HCT-116 cells. The cells were treated with DKL in various concentrations (32 and 50 μM) for 24 h and then analyzed for various experiments. MTT (tetrazolium bromide) and crystal violet assay investigated DKL-mediated cytotoxicity. Dichlorodihydrofluorescein diacetate staining was used to assess the reactive oxygen species (ROS) measurement, and apoptotic changes were studied by dual acridine orange and ethidium bromide staining. Protein expression of cell survival, cell cycle, proliferation, and apoptosis protein was evaluated by western blot analysis. Results indicated that DKL produces significant cytotoxicity in HCT-116, and the half-maximal inhibitory concentration was found to be 32 μM for 24-h incubation. Moreover, effective production of ROS and enhanced apoptotic signs were observed upon DKL treatment in HCT-116. DKL induces the expression of phosphorylated PI3K, AKT, and mToR-associated enhanced expression of cyclin-D1, proliferating cell nuclear antigen, cyclin-dependent kinase (CDK)-4, CDK-6, and Bcl-2 in HCT-116. In addition, proapoptotic proteins such as Bax, caspase-9, and caspase-3 were significantly enhanced by DKL treatment in HCT-116. Hence, DKL has been considered a chemotherapeutic drug by impeding the expression of PI3K-, AKT-, and mTOR-mediated inhibition of proliferation and cell cycle-regulating proteins.     

产肠毒素大肠杆菌诱导肠上皮细胞凋亡的研究进展

产肠毒素大肠杆菌(enterotoxigenic Escherichia coli, ETEC)是引起人和动物腹泻的重要病原菌之一,其中黏附素和肠毒素是其感染引起腹泻的主要毒力因子。首先,黏附素介导ETEC与宿主小肠上皮细胞的黏附和定殖。随后,定殖的细菌产生肠毒素,导致水、电解质代谢紊乱,最终引起水样腹泻。传统的观点认为ETEC属于非侵袭性大肠杆菌,并不会引起肠上皮细胞凋亡和破坏肠道的屏障结构。但是越来越多的研究证据表明,在体外和体内ETEC感染均可诱导肠上皮细胞凋亡,破坏宿主肠黏膜屏障的完整性,促进疾病发展。本文将就ETEC不同毒力因子诱导细胞凋亡的具体机制、细胞凋亡与疾病发展的相关性以及在临床如何利用抗凋亡治疗预防ETEC感染等方面进行综述,旨为进一步深入阐明ETEC的分子致病机制提供参考,为防治ETEC引起的腹泻提供新策略。     

RNF7 promotes glioma growth via the PI3K/AKT signalling axis

RNF7 has been reported to play critical roles in various cancers. However, the underlying mechanisms of RNF7 in glioma development remain largely unknown. Herein, the expression level of RNF7 was examined in tissues by quantitative real-time PCR, Western blotting and immunohistochemistry. The effect of RNF7 on glioma progression was measured by performing CCK-8 and apoptosis assays, cell cycle-related experiments and animal experiments. The effect of RNF7 on PI3K/AKT signalling pathway was tested by Western blotting. First, we found that RNF7 was upregulated in tumour tissue compared with normal brain tissue, especially in high-grade glioma, and the high expression of RNF7 was significantly related to tumour size, Karnofsky Performance Scale score and a poor prognosis. Second, RNF7 overexpression facilitated tumour cell cycle progression and cell proliferation and suppressed apoptosis. Conversely, RNF7 knockdown suppressed tumour cell cycle progression and cell proliferation and facilitated apoptosis. Furthermore, follow-up mechanistic studies indicated that RNF7 could facilitate glioma cell proliferation and cell cycle progression and inhibit apoptosis by activating the PI3K/AKT signalling pathway. This study shows that RNF7 can clearly promote glioma cell proliferation by facilitating cell cycle progression and inhibiting apoptosis by activating the PI3K/AKT signalling pathway. Targeting the RNF7/PI3K/AKT axis may provide a new perspective on the prevention or treatment of glioma.     

Monocarbonyl Analogs of Curcumin with Potential to Treat Colorectal Cancer

Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile.     

Antiproliferative Potential of Olneya tesota PF2 Lectin in Human Acute Monocytic Leukemia Cells

Acute monocytic leukemia is a type of myeloid leukemia that develops in monocytes. The current clinical therapies for leukemia are unsatisfactory due to their side effects and nonspecificity toward target cells. Some lectins display antitumor activity and may specifically recognize cancer cells by binding to carbohydrate structures on their surface. Therefore, this study evaluated the response of the human monocytic leukemia cell lines THP-1 to the Olneya tesota PF2 lectin. The induction of apoptosis and reactive oxygen species production in PF2-treated cells was evaluated by flow cytometry, and the lectin-THP-1 cell interaction and mitochondrial membrane potential were evaluated by confocal fluorescence microscopy. PF2 genotoxicity was evaluated by DNA fragmentation analysis via gel electrophoresis. The results showed that PF2 binds to THP-1 cells, triggers apoptosis and DNA degradation, changes the mitochondrial membrane potential, and increases reactive oxygen species levels in PF2-treated THP-1 cells. These results suggest the potential use of PF2 for developing alternative anticancer treatments with enhanced specificity.     

Sesquiterpenoids from the Resina Commiphora Promoting the Apoptotic Activity of PC-3 Prostate Cancer Cells

Four new germacrane-type sesquiterpenes commiphoranes M1-M4 ( 1 - 4 ) together with eighteen sesquiterpenes were isolated from the Resina Commiphora. The structures and relative configurations of new substances were determined by using spectroscopic methods. Biological activity investigation revealed that nine compounds including 7 , 9 , 14 , 16 , (+)- 17 , (−)- 17 , 18 , 19 , and 20 could induce the apoptosis of prostate cancer originated PC-3 cells, through classic apoptosis signaling pathway, even using flow cytometry showed that the compound (+)- 17 caused apoptosis of PC-3 cells more than 40 %, suggesting their potential therapeutic application in the development of novel drugs against prostate cancer.     

T cell receptor specific apoptosis: an endogenous mechanism for T cell homeostasis and potential strategy for antigen modulation of disease

T lymphocytes can undergo an activation/proliferation response or an apoptotic response following T cell receptor engagement. The choice between these outcomes is dictated by the activation state of the T lymphocyte, the presence of interleukin-2 and the strength of the T cell receptor stimulus. Specifically, when quiescent cells encounter effectively presented antigen they are activated and begin to proliferate. In contrast, activated cells, moving through the cell cycle under the influence of IL-2, undergo apoptosis upon reencountering antigen. Both the tumour necrosis factor receptor and CD95 (FAS) are known to participate in mediating this cell death. Genetic defects in the molecules of the lymphocyte death pathway (CD95, FAS ligand, IL-2 receptor) lead to syndromes of autoimmunity and dysregulated lymphocyte homeostasis. An understanding of the principles of the autocrine feedback death model can provide the rationale basis for effective antigen specific modulation of T cell mediated disease processes.     

Cell cycle and cell size dependence of susceptibility to hydrodynamic forces

Exposure of animal cells to intense hydrodynamic forces exerted in turbulent capillary flow, and by controiled agitation and aeration, resulted in preferential destruction of S and G(2) cells and the extent of destruction of these cells was dependent upon the intensity of the action. The loss of these cells was possibly due to their larger size. However, the appearance of large numbers of membrane-bound vesicular structures similar to apoptotic bodies as well as cells with low DNA stainability (in a sub-G(1) peak) suggested that the action of adverse hydrodynamic forces on these large cells may at least in part be to induce an apoptotic response. (c) 1995 John Wiley & Sons, Inc.