11,847 results match your criteria bcl-2 family


Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis.

Cell Death Dis 2021 May 12;12(5):474. Epub 2021 May 12.

Department of Gastroenterology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, 510630, China.

Fas/Fas ligand (FasL)-mediated cell apoptosis involves a variety of physiological and pathological processes including chronic hepatic diseases, and hepatocytes apoptosis contributes to the development of liver fibrosis following various causes. However, the mechanism of the Fas/FasL signaling and hepatocytes apoptosis in liver fibrogenesis remains unclear. The Fas/FasL signaling and hepatocytes apoptosis in liver samples from both human sections and mouse models were investigated. Read More

View Article and Full-Text PDF

Selective BCL-X Antagonists Eliminate Infected Cells from a Primary Cell Model of HIV Latency but not from Reservoirs.

J Virol 2021 May 12. Epub 2021 May 12.

Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York NY, USA.

HIV persists, despite immune responses and antiretroviral therapy, in viral reservoirs that seed rebound viremia if therapy is interrupted. Previously, we showed that the BCL-2 protein contributes to HIV persistence by conferring a survival advantage to reservoir-harboring cells. Here, we demonstrate that many of the BCL-2 family members are overexpressed in HIV-infected CD4 T-cells, indicating increased tension between pro-apoptotic and pro-survival family members - and suggesting that inhibition of pro-survival members may disproportionately affect the survival of HIV-infected cells. Read More

View Article and Full-Text PDF

Apoptosis is not conserved in plants as revealed by critical examination of a model for plant apoptosis-like cell death.

BMC Biol 2021 May 12;19(1):100. Epub 2021 May 12.

Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences and Linnean Center for Plant Biology, P.O. Box 7015, SE-750 07, Uppsala, Sweden.

Background: Animals and plants diverged over one billion years ago and evolved unique mechanisms for many cellular processes, including cell death. One of the most well-studied cell death programmes in animals, apoptosis, involves gradual cell dismantling and engulfment of cellular fragments, apoptotic bodies, through phagocytosis. However, rigid cell walls prevent plant cell fragmentation and thus apoptosis is not applicable for executing cell death in plants. Read More

View Article and Full-Text PDF

Virus-mediated inactivation of anti-apoptotic Bcl-2 family members promotes Gasdermin-E-dependent pyroptosis in barrier epithelial cells.

Immunity 2021 May 5. Epub 2021 May 5.

Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA; Program in Immunology, Harvard Medical School, Longwood Avenue, Boston, MA, USA. Electronic address:

Two sets of innate immune proteins detect pathogens. Pattern recognition receptors (PRRs) bind microbial products, whereas guard proteins detect virulence factor activities by the surveillance of homeostatic processes within cells. While PRRs are well known for their roles in many types of infections, the role of guard proteins in most infectious contexts remains less understood. Read More

View Article and Full-Text PDF

ZBP1 not RIPK1 mediates tumor necroptosis in breast cancer.

Nat Commun 2021 May 11;12(1):2666. Epub 2021 May 11.

National Cancer Institute; National Institutes of Health, Laboratory of Immune Cell Biology, Bethesda, MD, USA.

Tumor necrosis happens commonly in advanced solid tumors. We reported that necroptosis plays a major role in tumor necrosis. Although several key necroptosis regulators including receptor interacting protein kinase 1 (RIPK1) have been identified, the regulation of tumor necroptosis during tumor development remains elusive. Read More

View Article and Full-Text PDF

CircRNA_2646 functions as a ceRNA to promote progression of esophageal squamous cell carcinoma via inhibiting miR-124/PLP2 signaling pathway.

Cell Death Discov 2021 May 11;7(1):99. Epub 2021 May 11.

Department of Thoracic Surgery, the First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, China.

MicroRNA-124 (miR-124) has been predicted as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). However, factors contributing to miR-124 reduction remain unclear. Circular RNAs (circRNAs) are a new family of non-coding RNAs with gene regulatory potential via interacting with miRNAs. Read More

View Article and Full-Text PDF

Obatoclax, the pan-Bcl-2 inhibitor sensitizes hepatocellular carcinoma cells to promote the anti-tumor efficacy in combination with immune checkpoint blockade.

Transl Oncol 2021 May 8;14(8):101116. Epub 2021 May 8.

Department of anesthesiology, Linyi Central Hospital, Shandong 276400, China. Electronic address:

Bcl-2 family proteins play critical roles in regulating lymphocyte development and maintain homeostasis, and have also been proved to be involved in various cancer types development. However, the role of Bcl-2 in hepatocellular carcinoma (HCC) development has not been clearly studied. Here, we reported the pan-Bcl-2 inhibitor, obatoclax could directly inhibit HCC growth in vitro. Read More

View Article and Full-Text PDF

Novel antimicrobial anionic cecropins from the spruce budworm feature a poly-L-aspartic acid C-terminus.

Proteins 2021 May 11. Epub 2021 May 11.

Institut de biologie intégrative et des systèmes (IBIS) and Faculté de médecine, Université Laval, Quebec City, Canada.

Cecropins form a family of amphipathic α-helical cationic peptides with broad-spectrum antibacterial properties and potent anticancer activity. The emergence of bacteria and cancer cells showing resistance to cationic antimicrobial peptides (CAMPs) has fostered a search for new, more selective and more effective alternatives to CAMPs. With this goal in mind, we looked for cecropin homologs in the genome and transcriptome of the spruce budworm, Choristoneura fumiferana. Read More

View Article and Full-Text PDF

Effects of Amyloid Precursor Protein Overexpression on NF-κB, Rho-GTPase and Pro-Apoptosis Bcl-2 Pathways in Neuronal Cells.

Rep Biochem Mol Biol 2021 Jan;9(4):417-425

Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur, Malaysia.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that causes cognitive dysfunction. Previous studies have suggested that amyloid plaques, mainly comprising of amyloid-beta peptides, play a pivotal role in AD pathophysiology. This study focuses on the evaluation of the effects of amyloid precursor protein (APP) overexpression on NF-κB, Rho-GTPase and Bcl-2 mediated pro-apoptotic pathways in neuronal cells. Read More

View Article and Full-Text PDF
January 2021

Structure-based design approach of potential BCL-2 inhibitors for cancer chemotherapy.

Comput Biol Med 2021 Apr 30;134:104455. Epub 2021 Apr 30.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bengaluru, 560054, Karnataka, India. Electronic address:

B-cell lymphoma 2 (BCL-2) family is one of the chief regulators of cellular apoptosis. The intricate interactions between pro-apoptotic and anti-apoptotic genes of the BCL-2 family dictate the apoptotic balance of the cell. An overexpression of the anti-apoptotic members of BCL-2 is indicative of cell death evasion and cancer metastasis. Read More

View Article and Full-Text PDF

Novel CTRP8-RXFP1-JAK3-STAT3 axis promotes Cdc42-dependent actin remodeling for enhanced filopodia formation and motility in human glioblastoma cells.

Mol Oncol 2021 May 7. Epub 2021 May 7.

Depts. of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada.

CTRP8 is the least studied member of the C1Q-TNF related peptide family. We identified CTRP8 as a ligand of the G protein coupled receptor RXFP1 in glioblastoma multiforme (GBM). The CTRP8-RXFP1 ligand-receptor system protects human GBM cells against the DNA alkylating damage inducing temozolomide (TMZ), the drug of choice for the treatment of patients with GBM. Read More

View Article and Full-Text PDF

PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial ischemia/reperfusion injury.

J Mol Histol 2021 May 5. Epub 2021 May 5.

Department of Thoracic Surgery, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.

Myocardial ischemia/reperfusion (I/R) injury induces cardiomyocyte apoptosis to deteriorate heart function. Thus, how to inhibit cardiomyocyte apoptosis is the focus of recent researches. Proteasome family member PSMB4 (proteasome subunit beta type-4) promotes cell survival. Read More

View Article and Full-Text PDF

Gold Cluster Capped with a BCL-2 Antagonistic Peptide Exerts Synergistic Antitumor Activity in Chronic Lymphocytic Leukemia Cells.

ACS Appl Mater Interfaces 2021 May 4;13(18):21108-21118. Epub 2021 May 4.

Department of Chemistry and Biology, Faculty of Environment and Life Science, Beijing University of Technology, Beijing 100124, China.

Chronic lymphocytic leukemia (CLL) is still incurable by conventional chemotherapy due to the resistance to apoptosis. We have previously found that a peptide-capped gold cluster (AuSv) can target on the aberrant oxidative stress in CLL cells to specially inhibit thioredoxin reductase (TrxR) activity, resulting in significant apoptosis. However, the required doses of the gold cluster for inducing apoptosis are high, restricting its potential for further applications. Read More

View Article and Full-Text PDF

Pharmacological Targeting of Executioner Proteins: Controlling Life and Death.

J Med Chem 2021 May 3;64(9):5276-5290. Epub 2021 May 3.

Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1J7, Canada.

Small-molecule mediated modulation of protein interactions of Bcl-2 (B-cell lymphoma-2) family proteins was clinically validated in 2015 when Venetoclax, a selective inhibitor of the antiapoptotic protein BCL-2, achieved breakthrough status designation by the FDA for treatment of lymphoid malignancies. Since then, substantial progress has been made in identifying inhibitors of other interactions of antiapoptosis proteins. However, targeting their pro-apoptotic counterparts, the "executioners" BAX, BAK, and BOK that both initiate and commit the cell to dying, has lagged behind. Read More

View Article and Full-Text PDF

PCR array analysis identified hyperproliferation but not autophagy or apoptosis in fibrous epulis.

J Clin Lab Anal 2021 May 2:e23784. Epub 2021 May 2.

Department of Stomatology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

Background: The pathogenesis of fibrous epulis is still quite unclear. Our recent genome-wide RNA sequencing analysis revealed that in fibrous epulis, RAS-PI3K-AKT-NF-κB pathway regulates the expression of Bcl-2 family and IAP family genes, leading to increased proliferation and the inhibition of apoptosis. The PI3K/AKT signaling pathway can promote autophagy in human gingival fibroblasts; therefore, the purpose of the present study was to identify whether autophagy is involved in the pathogenesis of fibrous epulis. Read More

View Article and Full-Text PDF

Downregulation of miR-383 reduces depression-like behavior through targeting Wnt family member 2 (Wnt2) in rats.

Sci Rep 2021 Apr 29;11(1):9223. Epub 2021 Apr 29.

Department of Psychiatry, Qingdao Mental Health Center, Qingdao University, No. 299 Nanjing Road, Qingdao City, 266000, Shandong Province, People's Republic of China.

This study aimed to evaluate the role of miR-383 in the regulation of Wnt-2 signaling in the rat model of chronic stress. The male SD rats with depressive-like behaviors were stimulated with chronic unpredictable mild stress (CUMS) including ice-water swimming for 5 min, food deprivation for 24 h, water deprivation for 24 h, stimulating tail for 1 min, turning night into day, shaking for 15 min (once/s), and wrap restraint (5 min/time) every day for 21 days. The expression levels of miRNAs were detected by qRT-PCR, and the expression levels of Wnt2, depression-impacted proteins (GFAP, BDNF, CREB), brain neurotransmitters (5-HT, NE, DA) and apoptosis-related proteins (Bax and Bcl-2) were evaluated by qRT-PCR and western blot. Read More

View Article and Full-Text PDF

Intrinsically Connected: Therapeutically Targeting the Cathepsin Proteases and the Bcl-2 Family of Protein Substrates as Co-regulators of Apoptosis.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Trubetskaya str. 8-2, 119991 Moscow, Russia.

Taken with the growing importance of cathepsin-mediated substrate proteolysis in tumor biology and progression, the focus and emphasis placed on therapeutic design and development is coming into fruition. Underpinning this approach is the invariable progression from the direction of fully characterizing cathepsin protease members and their substrate targets, towards targeting such an interaction with tangible therapeutics. The two groups of such substrates that have gained much attention over the years are the pro- and anti- apoptotic protein intermediates from the extrinsic and intrinsic signaling arms of the apoptosis pathway. Read More

View Article and Full-Text PDF

Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells.

Int J Mol Sci 2021 Apr 20;22(8). Epub 2021 Apr 20.

Department of Biochemistry, Cell and Molecular Biology & Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University, Ruská 87, 100 00 Prague, Czech Republic.

Pancreatic β-cell failure and death contribute significantly to the pathogenesis of type 2 diabetes. One of the main factors responsible for β-cell dysfunction and subsequent cell death is chronic exposure to increased concentrations of FAs (fatty acids). The effect of FAs seems to depend particularly on the degree of their saturation. Read More

View Article and Full-Text PDF

Leucine Reconstitutes Phagocytosis-Induced Cell Death in -Infected Neonatal Monocytes-Effects on Energy Metabolism and mTOR Signaling.

Int J Mol Sci 2021 Apr 20;22(8). Epub 2021 Apr 20.

Section of Neonatology, University Children's Hospital, Pauwelsstr. 30, 52074 Aachen, Germany.

MΦ differentiate from circulating monocytes (Mo). The reduced ability of neonatal Mo to undergo apoptosis after infection (phagocytosis-induced cell death (PICD)) could contribute to sustained inflammatory processes. The objective of our study was to investigate whether immune metabolism in Mo can be modified to gain access to pro-apoptotic signaling. Read More

View Article and Full-Text PDF

Ampelopsin Inhibits Cell Proliferation and Induces Apoptosis in HL60 and K562 Leukemia Cells by Downregulating AKT and NF-κB Signaling Pathways.

Int J Mol Sci 2021 Apr 20;22(8). Epub 2021 Apr 20.

Department of Life Science and Biochemical Engineering, Sun Moon University, Asan 31460, Korea.

Leukemia is a type of blood cancer caused by the rapid proliferation of abnormal white blood cells. Currently, several treatment options, including chemotherapy, radiation therapy, and bone marrow transplantation, are used to treat leukemia, but the morbidity and mortality rates of patients with leukemia are still high. Therefore, there is still a need to develop more selective and less toxic drugs for the effective treatment of leukemia. Read More

View Article and Full-Text PDF

Contribution of Yeast Studies to the Understanding of BCL-2 Family Intracellular Trafficking.

Int J Mol Sci 2021 Apr 15;22(8). Epub 2021 Apr 15.

Institut de Biochimie et de Génétique Cellulaires, Université de Bordeaux, CNRS, UMR 5095, 1 Rue Camille Saint-Saëns, 33077 Bordeaux, France.

BCL-2 family members are major regulators of apoptotic cell death in mammals. They form an intricate regulatory network that ultimately regulates the release of apoptogenic factors from mitochondria to the cytosol. The ectopic expression of mammalian BCL-2 family members in the yeast which lacks BCL-2 homologs, has been long established as a useful addition to the available models to study their function and regulation. Read More

View Article and Full-Text PDF

Autofluorescence Imaging of Treatment Response in Neuroendocrine Tumor Organoids.

Cancers (Basel) 2021 Apr 14;13(8). Epub 2021 Apr 14.

Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706, USA.

Gastroenteropancreatic neuroendocrine tumors (GEP-NET) account for roughly 60% of all neuroendocrine tumors. Low/intermediate grade human GEP-NETs have relatively low proliferation rates that animal models and cell lines fail to recapitulate. Short-term patient-derived cancer organoids (PDCOs) are a 3D model system that holds great promise for recapitulating well-differentiated human GEP-NETs. Read More

View Article and Full-Text PDF

Bcl-2 Family of Proteins in the Control of Mitochondrial Calcium Signalling: An Old Chap with New Roles.

Int J Mol Sci 2021 Apr 2;22(7). Epub 2021 Apr 2.

Université de Lyon, Centre de Recherche en Cancérologie de Lyon, U1052 INSERM, UMR CNRS 5286, Université Lyon I, Centre Léon Bérard, 28 rue Laennec, 69008 Lyon, France.

Bcl-2 family proteins are considered as one of the major regulators of apoptosis. Indeed, this family is known to control the mitochondrial outer membrane permeabilization (MOMP): a central step in the mitochondrial pathway of apoptosis. However, in recent years Bcl-2 family members began to emerge as a new class of intracellular calcium (Ca) regulators. Read More

View Article and Full-Text PDF

Combination of PKCδ Inhibition with Conventional TKI Treatment to Target CML Models.

Cancers (Basel) 2021 Apr 2;13(7). Epub 2021 Apr 2.

Université Côte d'Azur, Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), 06204 Nice, France.

Numerous combinations of signaling pathway blockades in association with tyrosine kinase inhibitor (TKI) treatment have been proposed for eradicating leukemic stem cells (LSCs) in chronic myeloid leukemia (CML), but none are currently clinically available. Because targeting protein kinase Cδ (PKCδ) was demonstrated to eliminate cancer stem cells (CSCs) in solid tumors, we evaluated the efficacy of PKCδ inhibition in combination with TKIs for CML cells. We observed that inhibition of PKCδ by a pharmacological inhibitor, by gene silencing, or by using K562 CML cells expressing dominant-negative (DN) or constitutively active (CA) PKCδ isoforms clearly points to PKCδ as a regulator of the expression of the stemness regulator BMI1. Read More

View Article and Full-Text PDF

Krüppel-Like Factor 4 and Its Activator APTO-253 Induce NOXA-Mediated, p53-Independent Apoptosis in Triple-Negative Breast Cancer Cells.

Genes (Basel) 2021 Apr 8;12(4). Epub 2021 Apr 8.

Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo 113-0033, Japan.

Inducing apoptosis is an effective treatment for cancer. Conventional cytotoxic anticancer agents induce apoptosis primarily through activation of tumor suppressor p53 by causing DNA damage and the resulting regulation of B-cell leukemia/lymphoma-2 (BCL-2) family proteins. Therefore, the effects of these agents are limited in cancers where p53 loss-of-function mutations are common, such as triple-negative breast cancer (TNBC). Read More

View Article and Full-Text PDF

Effects of Epstein-Barr Virus Infection on the Risk and Prognosis of Primary Laryngeal Squamous Cell Carcinoma: A Hospital-Based Case-Control Study in Taiwan.

Cancers (Basel) 2021 Apr 6;13(7). Epub 2021 Apr 6.

Faculty of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan.

Mounting molecular evidence supports Epstein-Barr virus (EBV) involvement in the pathogenesis of laryngeal squamous cell carcinoma (LSCC); however, the epidemiological data are inconsistent. In this retrospective case-control study, we aimed to determine whether EBV infection underlies the risk and prognosis of LSCC. The prevalence of EBV infection, as analyzed using an EBV DNA polymerase chain reaction assay, was significantly higher in 42 Taiwanese patients with newly diagnosed primary LSCC, compared to 39 age- and sex-matched control patients without cancer (48% vs. Read More

View Article and Full-Text PDF

BH3 Mimetic Sensitivity of Colorectal Cancer Cell Lines in Correlation with Molecular Features Identifies Predictors of Response.

Int J Mol Sci 2021 Apr 7;22(8). Epub 2021 Apr 7.

Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Colorectal cancer (CRC) is a heterogeneous disease, which in part explains the differential response to chemotherapy observed in the clinic. BH3 mimetics, which target anti-apoptotic BCL-2 family members, have shown potential in the treatment of hematological malignancies and offer promise for the treatment of solid tumors as well. To gain a comprehensive understanding of the response to BH3 mimetics in CRC and the underlying molecular factors predicting sensitivity, we screened a panel of CRC cell lines with four BH3 mimetics targeting distinct anti-apoptotic BCL-2 proteins. Read More

View Article and Full-Text PDF

Molecular mechanisms underlying antitumor activity of camel whey protein against multiple myeloma cells.

Saudi J Biol Sci 2021 Apr 28;28(4):2374-2380. Epub 2021 Jan 28.

Department of Biochemistry, College of Science, King Saud University, PO Box 22452, Riyadh 11451, Saudi Arabia.

Treating drug-resistant cancer cells is a clinical challenge and it is also vital to screen for new cancer drugs. Multiple myeloma (MM) is a plasma cell clonal cancer that, despite many experimental therapeutics, remains incurable. In this study, two MM cell line lines U266 and RPMI 8226 were used to determine the impact of camel whey protein (CWP). Read More

View Article and Full-Text PDF

Structure-Guided Development of Potent Benzoylurea Inhibitors of BCL-X and BCL-2.

J Med Chem 2021 May 27;64(9):5447-5469. Epub 2021 Apr 27.

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia.

The BCL-2 family of proteins (including the prosurvival proteins BCL-2, BCL-X, and MCL-1) is an important target for the development of novel anticancer therapeutics. Despite the challenges of targeting protein-protein interaction (PPI) interfaces with small molecules, a number of inhibitors (called BH3 mimetics) have entered the clinic and the BCL-2 inhibitor, ABT-199/venetoclax, is already proving transformative. For BCL-X, new validated chemical series are desirable. Read More

View Article and Full-Text PDF

Targeting the metabolic vulnerability of acute myeloid leukemia blasts with a combination of venetoclax and 8-chloro-adenosine.

J Hematol Oncol 2021 Apr 26;14(1):70. Epub 2021 Apr 26.

Hematology Malignancies Research Institute, Gehr Family Center for Leukemia Research, City of Hope Medical Center, Kaplan CRB, 1026, 1500 East Duarte Road, Duarte, CA, 91010, USA.

Background: BCL-2 inhibition through venetoclax (VEN) targets acute myeloid leukemia (AML) blast cells and leukemic stem cells (LSCs). Although VEN-containing regimens yield 60-70% clinical response rates, the vast majority of patients inevitably suffer disease relapse, likely because of the persistence of drug-resistant LSCs. We previously reported preclinical activity of the ribonucleoside analog 8-chloro-adenosine (8-Cl-Ado) against AML blast cells and LSCs. Read More

View Article and Full-Text PDF