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intrinsic apoptosis pathway

Saranya Satitmanwiwat, Chinarat Changsangfa, Anuson Khanuengthong, Kornkanok Promthep, Sittiruk Roytrakul, Teerakul Arpornsuwan, Kulnasan Saikhun, Hathaitip Sritanaudomchai
AIM: This study aimed to investigate the mechanism of the induction of apoptosis of human oral cancer cells by the scorpion venom peptide BmKn2. METHODS: Human oral squamous carcinoma cells (HSC4), mouth epidermoid carcinoma cells (KB), human normal gingival cells (HGC) and dental pulp cells (DPC) were treated with BmKn-2 peptide for 24h. Cell viability was determined by the MTT assay. Apoptosis was assessed using phase contrast microscopy, by propidium iodide (PI) staining to assess nuclear morphology and by Annexin V staining...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xinmin Zhao, Xianghua Wu, Wen Yu, Xuwei Cai, Qi Liu, Xiaolong Fu, Zhebin Liu, Dali Hu, Shiyun Pan, Qiling Huang
The present study examined the potential of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) to inhibit proliferation and induce apoptosis in non‑small‑cell lung cancer (NSCLC) cell lines. It also investigated its mechanisms of action in different genotypes of human NSCLC. A total of three NSCLC cell lines, PC‑9, A549, and NCI‑H1975, were treated with PA‑MSHA at different concentrations. The anti‑proliferative effect of PA‑MSHA was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay...
October 20, 2016: Molecular Medicine Reports
Patrick Antonietti, Benedikt Linder, Stephanie Hehlgans, Iris C Mildenberger, Michael C Burger, Simone Fulda, Joachim P Steinbach, Florian Gessler, Franz Rodel, Michel Mittelbronn, Donat Kogel
Malignant gliomas exhibit a high intrinsic resistance against stimuli triggering apoptotic cell death. HSF1 (heat shock factor 1) acts as transcription factor upstream of HSP70 and the HSP70 co-chaperone BAG3 that is overexpressed in glioblastoma. To specifically target this resistance mechanism, we applied the selective HSF1 inhibitor KRIBB11 and the HSP70/BAG3 interaction inhibitor YM-1 in combination with the pan-Bcl-2 inhibitor AT-101. Here we demonstrate that lentiviral BAG3 silencing significantly enhances AT-101-induced cell death and reactivates effector caspase-mediated apoptosis in U251 glioma cells with high BAG3 expression, while these sensitizing effects were less pronounced in U343 cells expressing lower BAG3 levels...
October 24, 2016: Molecular Cancer Therapeutics
Wipada Duangprompo, Kalaya Aree, Arunporn Itharat, Pintusorn Hansakul
5,6-dihydroxy-2,4-dimethoxy-9,10-dihydrophenanthrene (HMP) is an active compound isolated from the rhizome extracts of Dioscorea membranacea Pierre, a Thai medicinal plant. This study aimed to investigate the growth-inhibitory and apoptosis-inducing effects of HMP in human lung cancer A549 cells. The antiproliferative and cytotoxic effects of HMP were analyzed by a Sulforhodamine B assay. Cell division, cell cycle distribution and membrane asymmetry changes were each performed with different fluorescent dyes and then analyzed by flow cytometry...
October 25, 2016: American Journal of Chinese Medicine
Himanshi Kapoor, Nalini Yadav, Madhu Chopra, Sushil Chandra Mahapatra, Veena Agrawal
Glioblastoma has been reckoned as the prime cause of death due to brain tumours, being most invasive and lethal. Available treatment options, i.e. surgery, radiotherapy, chemotherapy and targeted therapies are not effective in improving prognosis, so an alternate therapy is insistent. Plant based drugs are efficient due to their synergistic action, multi-targeted approach and least side effects. Present investigation reports the strong anti-tumorous potential of Nardostachys jatamansi rhizome extract (NJRE) on U87 MG glioblastoma cells...
October 19, 2016: Current Cancer Drug Targets
Stefan M Ivanov, Roland G Huber, Jim Warwicker, Peter J Bond
Critical regulatory pathways are replete with instances of intra- and interfamily protein-protein interactions due to the pervasiveness of gene duplication throughout evolution. Discerning the specificity determinants within these systems has proven a challenging task. Here, we present an energetic analysis of the specificity determinants within the Bcl-2 family of proteins (key regulators of the intrinsic apoptotic pathway) via a total of ∼20 μs of simulation of 60 distinct protein-protein complexes. We demonstrate where affinity and specificity of protein-protein interactions arise across the family, and corroborate our conclusions with extensive experimental evidence...
October 17, 2016: Structure
Alfredo Lagunas-Martínez, Enrique García-Villa, Magaly Arellano-Gaytán, Carla O Contreras-Ochoa, Jisela Dimas-González, María E López-Arellano, Vicente Madrid-Marina, Patricio Gariglio
The E6 oncoprotein can interfere with the ability of infected cells to undergo programmed cell death through the proteolytic degradation of proapoptotic proteins such as p53, employing the proteasome pathway. Therefore, inactivation of the proteasome through MG132 should restore the activity of several proapoptotic proteins. We investigated whether in HPV16 E6-expressing keratinocytes (KE6 cells), the restoration of p53 levels mediated by MG132 and/or activation of the CD95 pathway through apoptosis antigen-1 (APO-1) antibody are responsible for the induction of apoptosis...
October 20, 2016: Apoptosis: An International Journal on Programmed Cell Death
Ziyou Wang, Hua Zhang, Jiahui Zhou, Xiangning Zhang, Liyong Chen, Kangxing Chen, Zunnan Huang
Hepatocellular carcinoma is a lethal cancer with high recurrence ratio and lacks effective therapeutics. In the past few years, it has been reported that increased intake of vegetables and fruits could reduce the cancer incidence, which suggests dietary agents might possess anticancer effects. Eriocitrin is a flavonoid isolated from lemon, which is known as a strong antioxidant agent. We here for the first time demonstrated that eriocitrin could inhibit the proliferation of hepatocellular carcinoma cell lines by arresting cell cycle in S phase through up-regulation of p53, cyclin A, cyclin D3 and CDK6...
October 20, 2016: Cancer Chemotherapy and Pharmacology
Yaoyao Shi, Yue Kuai, Lizhen Lei, Yuanyuan Weng, Friederike Berberich- Siebelt, Xinxia Zhang, Jinjie Wang, Yuan Zhou, Xin Jiang, Guoping Ren, Hongyang Pan, Zhengrong Mao, Ren Zhou
Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6...
October 15, 2016: Oncotarget
Yi Chen, Junsheng Lin
As an indispensable process of cell life, apoptosis is essential for keeping homeostasis at cell level. Dysregulation of apoptosis is usually involved in the pathological processes of many complex diseases including cancer. With the properties such as high affinity and specificity to their targets, easy of synthesis and modification and good biocompatibility, aptamers have been attractive molecules applied in basic research, diagnostics and therapeutics. This review mainly focuses on the recent researches on application of aptamers in interference of cell apoptosis...
October 14, 2016: Biochimie
Lin Xu, Zhu Wang, Shan-Yang He, Su-Fen Zhang, Hong-Jiao Luo, Kai Zhou, Xiao-Fei Li, Shao-Peng Qiu, Kai-Yuan Cao
Prostate cancer (PCa) is one of the most common malignant tumors and the second leading cause of cancer-related death among males. Bax-interacting factor-1 (Bif-1) is a member of Endophilin family, which binds to and activates the BAX protein in response to the apoptosis signaling pathway. Loss of Bif-1 may suppress the intrinsic pathway of apoptosis and promote tumorigenesis, but there is also converse evidence that Bif-1 could in part be responsible for the tumorigenesis and the role of Bif-1 in PCa development is not clear...
October 14, 2016: Oncology Reports
Yuh-Feng Tsai, Ching-Wen Huang, Jo-Hua Chiang, Fuu-Jen Tsai, Yuan-Man Hsu, Chi-Cheng Lu, Chen-Yu Hsiao, Jai-Sing Yang
Gadolinium (Gd) compounds are important as magnetic resonance imaging (MRI) contrast agents, and are potential anticancer agents. However, no report has shown the effect of gadolinium chloride (GdCl3) on osteosarcoma in vitro. The present study investigated the apoptotic mechanism of GdCl3 on human osteosarcoma U-2 OS cells. Our results indicated that GdCl3 significantly reduced cell viability of U-2 OS cells in a concentration-dependent manner. GdCl3 led to apoptotic cell shrinkage and DNA fragmentation in U-2 OS cells as revealed by morphologic changes and TUNEL staining...
October 14, 2016: Oncology Reports
Elizabeth Thomas, Vidya Gopalakrishnan, Mahesh Hegde, Sujeet Kumar, Subhas S Karki, Sathees C Raghavan, Bibha Choudhary
Resveratrol is one of the most widely studied bioactive plant polyphenols which possesses anticancer properties. Previously we have reported synthesis, characterization and identification of a novel resveratrol analog, SS28. In the present study, we show that SS28 induced cytotoxicity in several cancer cell lines ex vivo with an IC50 value of 3-5 μM. Mechanistic evaluation of effect of SS28 in non-small cell lung cancer cell line (A549) and T-cell leukemic cell line (CEM) showed that it inhibited Tubulin polymerization during cell division to cause cell cycle arrest at G2/M phase of the cell cycle at 12-18 h time period...
October 17, 2016: Scientific Reports
Zhao Luo, Xue-Wei Cao, Chen Li, Miao-Dan Wu, Xu-Zhong Yang, Jian Zhao, Fu-Jun Wang
Cell-penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human-derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin-binding domain of HB-EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30...
October 14, 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
Fang Wang, Zhu-Liang Wei, Xian-Rui Sun, Qiang Zhang, Cai-Xia Zhang, Wen-Xin Jiang, Xiao Yan, Jia-Ning Liu, Xiao Yuan
The apoptosis of myoblast in response to excessive cyclic stretch is crucial in adaptive construction of skeletal muscles in orthopedic functional therapy. Mitochondria signaling pathway is the central links in the execution of the intrinsic apoptotic cascade, but its molecular mechanism in stretch-induced apoptosis in myoblasts remains incompletely understood. The aim of this study was to investigate the mechanobiological roles of caspase-9 and Apoptosis Inducing Factor (AIF), two important components in mitochondrial pathway, in stretch-induced apoptosis of myoblast...
October 13, 2016: Journal of Cellular Biochemistry
Yan Xiu, Wingel Y Xue, Allyn Lambertz, Mariah Leidinger, Katherine Gibson-Corley, Chen Zhao
Previously we have shown that loss of non-canonical NF-κB signaling impairs self-renewal of hematopoietic stem/progenitor cells (HSPCs). This prompted us to investigate whether persistent activation of the non-canonical NF-κB signaling will have supportive effects on HSPC self-renewal. NF-κB-inducing kinase (NIK) is an important kinase that mainly activates the non-canonical pathway through directly phosphorylating IKKα. In contrast to our expectations, constitutive activation of NIK in the hematopoietic system leads to bone marrow failure and postnatal lethality due to intrinsic impairment of HSPC self-renewal and extrinsic disruption of bone marrow microenvironment through enhancing osteoclastogenesis...
October 12, 2016: Stem Cells
Prabhakar Bastola, Lisa Neums, Frank J Schoenen, Jeremy Chien
Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family, has been associated with various cellular functions including endoplasmic reticulum-associated degradation (ERAD), Golgi membrane reassembly, autophagy, DNA repair, and cell division. Recent studies identified VCP and ubiquitin proteasome system (UPS) as synthetic lethal targets in ovarian cancer. Here, we describe the preclinical activity of VCP inhibitors in ovarian cancer. Results from our studies suggest that quinazoline-based VCP inhibitors initiate G1 cell cycle arrest, attenuate cap-dependent translation and induce programmed cell death via the intrinsic and the extrinsic modes of apoptosis...
September 28, 2016: Molecular Oncology
Jaime Stella Moses Richardson, Gautam Sethi, Guan Serm Lee, Sri Nurestri Abdul Malek
BACKGROUND: Cancer has been one of the leading causes of mortality in this era. Ruta angustifolia L. Pers has been traditionally used as an abortifacient, antihelmintic, emmenagogue and ophthalmic. In Malaysia and Singapore, the local Chinese community used it for the treatment of cancer. METHODS: In this study, the methanol and fractionated extracts (hexane, chloroform, ethyl acetate and water) of R. angustifolia were tested for its cytotoxicity using the sulforhodamide (SRB) cytotoxicity assay against HCT-116, A549, Ca Ski and MRC5 cell lines...
October 12, 2016: BMC Complementary and Alternative Medicine
Bei Liu, Ruili Sun, Hongbo Luo, Xueting Liu, Manli Jiang, Chuang Yuan, Li Yang, Jinyue Hu
Our previous study showed that TLR3 induces apoptosis via both death receptors and mitochondial in human endothelial cells. We report here that the activation of TLR4 induced dose- and time-dependent cell death in moncytic THP-1 cells. LPS treatment of THP-1 cells induced the activation of both caspase 8 and 9, suggesting the involvement of intrinsic and extrinsic apoptosis pathways. TNFα was induced by TLR4 activation at both mRNA and protein levels, but its neutralization did not down-regulated TLR4-induced cell death...
October 4, 2016: Immunobiology
Jürgen Fritsch, Ricarda Fickers, Jan Klawitter, Vinzenz Särchen, Philipp Zingler, Dieter Adam, Ottmar Janssen, Eberhard Krause, Stefan Schütze
During apoptosis induction by TNF, the extrinsic and intrinsic apoptosis pathways converge at the lysosomal-mitochondrial interface. Earlier studies showed that the lysosomal aspartic protease Cathepsin D (CtsD) cleaves Bid to tBid, resulting in the amplification of the initial apoptotic cascade via mitochondrial outer membrane permeabilization (MOMP).The goal of this study was to identify further targets for CtsD that might be involved in activation upon death receptor ligation. Using a proteomics screen, we identified the heat shock protein 90 (HSP90) to be cleaved by CtsD after stimulation of U937 or other cell lines with TNF, FasL and TRAIL...
October 3, 2016: Oncotarget
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