6,661 results match your criteria bcl-xl expression

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

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Paeoniflorin ameliorates ischemic injury in rat brain via inhibiting cytochrome c/caspase3/HDAC4 pathway.

Acta Pharmacol Sin 2021 May 11. Epub 2021 May 11.

CAS Key Laboratory of Receptor Research, Department of Neuropharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Paeoniflorin (PF), a bioactive monoterpene glucoside, has shown a variety of pharmacological effects such as anti-inflammation and autophagy modulation etc. In this study, we investigated whether and how PF exerted a protective effect against ischemic brain injury in vivo and in vitro. Primary rat cortical neurons underwent oxygen/glucose deprivation/reperfusion (OGD/R) for 90 min. Read More

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Depletion of MRPL35 inhibits gastric carcinoma cell proliferation by regulating downstream signaling proteins.

World J Gastroenterol 2021 Apr;27(16):1785-1804

Key Laboratory of Hui Ethnic Medicine Modernization of Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China.

Background: Gastric carcinoma (GC) is a digestive system disease with high morbidity and mortality. However, early clinical detection is difficult, and the therapeutic effect for advanced disease is not satisfactory. Thus, finding new tumor markers and therapeutic targets conducive to the treatment of GC is imperative. Read More

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Fish oil supplementation increases expression of mammary tumor apoptosis mediators and reduces inflammation in an obesity-associated HER-2 breast cancer model.

J Nutr Biochem 2021 May 6:108763. Epub 2021 May 6.

Department of Human Health and Nutritional Sciences, University of Guelph, Guelph ON, Canada, N1G 2W1. Electronic address:

Obesity is associated with inflammation and has been shown to increase breast cancer severity. The objective of this study was to examine the effect of FO supplementation in obesity-associated mammary tumorigenesis in the MMTV-neu(ndl)-YD5 mouse model of human epidermal growth factor receptor-2 positive BC. Female mice were fed one of three diets for 16 weeks: i) high fat diet [HF, % kacl: 41. Read More

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Pristimerin synergistically sensitizes conditionally reprogrammed patient derived-primary hepatocellular carcinoma cells to sorafenib through endoplasmic reticulum stress and ROS generation by modulating Akt/FoxO1/p27 signaling pathway.

Phytomedicine 2021 Jun 4;86:153563. Epub 2021 Apr 4.

Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, 510080 Guangzhou, China. Electronic address:

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated mortality worldwide. Sorafenib (SORA), as a first-line therapeutic drug, has been used to treat HCC, but resistance poses a major limitation on the efficacy of SORA chemotherapy. Pristimerin (PRIS), a natural bioactive component isolated from various plant species in the Celastraceae and Hippocrateaceae families, has been reported to exhibit outstanding antitumor effects in several types of cells in vitro. Read More

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Attenuation of inhibitory PAS domain protein-induced cell death by synthetic peptides derived from Mcl-1 transmenbrane domain.

Cell Death Discov 2021 May 4;7(1):92. Epub 2021 May 4.

Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku Sendai, 980-8578, Japan.

Expression of Inhibitory PAS domain protein (IPAS) induces apoptosis by inhibiting the anti-apoptotic activity of mitochondrial pro-survival proteins including Bcl-x and Mcl-1 through direct binding. Analysis to examine the IPAS-binding region in Bcl-x demonstrated that the C-terminal transmembrane (TM) domain is indispensable for the specific binding. A chimeric protein composed of the TM domain of Mcl-1 fused to the C-terminus of Citrine also exhibited a binding affinity to IPAS, and markedly attenuated apoptosis caused by the overexpression of Cerulean-IPAS in SH-SY5Y cells. Read More

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Metabolomics and transcriptomics indicated the molecular targets of copper to the pig kidney.

Ecotoxicol Environ Saf 2021 May 1;218:112284. Epub 2021 May 1.

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Copper poses huge environmental and public health concerns due to its widespread and persistent use in the past several decades. Although it is well established that at higher levels copper causes nephrotoxicity, the exact mechanisms of its toxicity is not fully understood. Therefore, this experimental study for the first time investigates the potential molecular mechanisms including transcriptomics, metabolomics, serum biochemical, histopathological, cell apoptosis and autophagy in copper-induced renal toxicity in pigs. Read More

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Targeting epigenetic mechanisms to overcome venetoclax resistance.

Biochim Biophys Acta Mol Cell Res 2021 May 1;1868(8):119047. Epub 2021 May 1.

University of Florida Health Cancer Center and University of Florida Department of Medicine, Division of Hematology and Oncology, Gainesville, FL 32610, United States of America. Electronic address:

The BH-3 mimetic venetoclax overcomes apoptosis and therapy resistance caused by high expression of BCL2 or loss of BH3-only protein function. Although a promising therapy for hematologic malignancies, increased expression of anti-apoptotic MCL-1 or BCL-XL, as well as other resistance mechanisms prevent a durable response to venetoclax. Recent studies demonstrate that agents targeting epigenetic mechanisms such as DNA methyltransferase inhibitors, histone deacetylase (HDAC) inhibitors, histone methyltransferase EZH2 inhibitors, or bromodomain reader protein inhibitors may disable oncogenic gene expression signatures responsible for venetoclax resistance. Read More

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Effects of Treadmill Exercise on the Expression Level of BAX, BAD, BCL-2, BCL-XL, TFAM, and PGC-1α in the Hippocampus of Thimerosal-Treated Rats.

Neurotox Res 2021 May 3. Epub 2021 May 3.

Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Thimerosal (THIM) induces neurotoxic changes including neuronal death and releases apoptosis inducing factors from mitochondria to cytosol. THIM alters the expression level of factors involved in apoptosis. On the other hand, the anti-apoptotic effects of exercise have been reported. Read More

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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

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ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis.

J Exp Clin Cancer Res 2021 Apr 30;40(1):150. Epub 2021 Apr 30.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing, 400016, Yuzhong District, China.

Background: Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. Read More

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Da Cheng Qi Decoction Alleviates Cerulein-Stimulated AR42J Pancreatic Acinar Cell Injury via the JAK2/STAT3 Signaling Pathway.

Evid Based Complement Alternat Med 2021 9;2021:6657036. Epub 2021 Apr 9.

Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Background: Acute pancreatitis (AP) is a common acute abdomen inflammation, characterized by the dysregulation of digestive enzyme production and secretion. Many studies have shown that Da Cheng Qi Decoction (DCQD) is a secure, effective prescription on AP. In this study, cerulein-stimulated AR42J cells damage model was established to further explore the feasibility and underlying mechanism of DCQD as a potential inhibitor of JAK2/STAT3 pathway for the treatment of AP. Read More

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ATF3 Promotes Arsenic-Induced Apoptosis and Oppositely Regulates DR5 and Bcl-xL Expression in Human Bronchial Epithelial Cells.

Int J Mol Sci 2021 Apr 19;22(8). Epub 2021 Apr 19.

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Institute of Engineering Biology and Health, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China.

Arsenic is one of the most common environmental pollutants eliciting serious public health issues; however, it is also a well-recognized chemotherapeutic agent for acute promyelocytic leukemia. The association between arsenic exposure and lung diseases has been established, but underlying molecular mechanisms are poorly defined. Here we investigated the toxicology of arsenic in airway epithelium. Read More

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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

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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

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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

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Low dose venetoclax as a single agent treatment of plasma cell malignancies harboring t(11;14).

Am J Hematol 2021 Apr 26. Epub 2021 Apr 26.

Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Approximately 20% of newly diagnosed multiple myeloma (NDMM) patients harbor t(11;14), a marker of inferior prognosis, resulting in up-regulation of CCND1. These patients respond to BCL2 inhibitor experimental drug venetoclax. Furthermore, t(11;14) is reported to be associated with increased BCL2/MCL1 ratio. Read More

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Apoptotic mechanisms of gastric cancer cells induced by isolated erinacine S through epigenetic histone H3 methylation of FasL and TRAIL.

Food Funct 2021 Apr 29;12(8):3455-3468. Epub 2021 Mar 29.

Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi, Taiwan.

Erinacine S, the new bioactive diterpenoid compound isolated from the ethanol extract of the mycelia of Hericium erinaceus, displays great health-promoting properties. However, the effects of erinacine S on inductive apoptosis in cancer cells such as gastric cancer and its molecular mechanisms remain unclear. Our results demonstrated that erinacine S treatment significantly induces cell apoptosis with increased ROS production in gastric cancer cells, but not in normal cells. Read More

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Generation of an induced pluripotent stem cell line SDQLCHi026-A from a hereditary tyrosinemia type I patient carrying compound heterozygote mutations in FAH gene.

Stem Cell Res 2021 Apr 9;53:102331. Epub 2021 Apr 9.

Pediatric Research Institute, Qilu Children's Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250022, China. Electronic address:

Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient diagnosed as hereditary tyrosinemia type I (HT1) caused by FAH gene mutation. Induced pluripotent stem cells (iPSCs) were developed using non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and MYC. The established iPSC line (SDQLCHi026-A) displayed pluripotent cell morphology, high expression levels of pluripotency markers, differentiation potential in vitro, normal karyotype, and remaining the original FAH gene mutation. Read More

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Genetic or pharmacological reduction of cholangiocyte senescence improves inflammation and fibrosis in the  mouse.

JHEP Rep 2021 Jun 27;3(3):100250. Epub 2021 Jan 27.

Division of Gastroenterology and Hepatology, and the Mayo Clinic Center for Cell Signaling in Gastroenterology, Mayo Clinic, Rochester, MN, 55905, USA.

Background & Aims: Cholangiocyte senescence is important in the pathogenesis of primary sclerosing cholangitis (PSC). We found that CDKN2A (p16), a cyclin-dependent kinase inhibitor and mediator of senescence, was increased in cholangiocytes of patients with PSC and from a PSC mouse model (multidrug resistance 2; ). Given that recent data suggest that a reduction of senescent cells is beneficial in different diseases, we hypothesised that inhibition of cholangiocyte senescence would ameliorate disease in mice. Read More

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The NLRP3-related inflammasome modulates pain behavior in a rat model of trigeminal neuropathic pain.

Life Sci 2021 Apr 13;277:119489. Epub 2021 Apr 13.

Department of Anesthesiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China. Electronic address:

Aims: Nod-like receptor family pyrin domain containing 3 (NLRP3) may play an important role in neuropathic pain. Treatment for trigeminal neuropathic pain remains a challenge, as common drugs either do not demonstrate beneficial therapeutic effects or induce intolerance in patients.

Main Methods: In a rat model of trigeminal neuropathic pain, pain caused by the malpositioning of dental implants is similar to that experienced by humans. Read More

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Xanthoceraside induces cell apoptosis through downregulation of the PI3K/Akt/Bcl-2/Bax signaling pathway in cell lines of human bladder cancer.

Indian J Pathol Microbiol 2021 Apr-Jun;64(2):294-301

Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.

Background: Xanthoceraside is a component obtained in the husks of Xanthoceras sorbifolia Bunge. Series of researches proved that xanthoceraside had functions of anti-inflammation and anti-tumor effects. However, the mechanisms of xanthoceraside against bladder cancer are unclear. Read More

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CRISPR screens identify a novel combination treatment targeting BCL-X and WNT signaling for KRAS/BRAF-mutated colorectal cancers.

Oncogene 2021 May 12;40(18):3287-3302. Epub 2021 Apr 12.

Medical Research Center, Genomic Medicine Institute, Seoul National University College of Medicine, Seoul, Korea.

Metastatic or recurrent colorectal cancer (CRC) patients require systemic chemotherapy, but the therapeutic options of targeted agents remain limited. CRC patients with KRAS or BRAF gene mutations exhibit a worse prognosis and are resistant to anti-EGFR treatment. Previous studies have shown that the expression of anti-apoptotic protein BCL-X is increased in CRC patients with KRAS/BRAF mutations, suggesting BCL-X as a therapeutic target for this subgroup. Read More

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Evaluating the inhibitory priority of Bcl-xL to Bad, tBid and Bax by using live-cell imaging assay.

Cytometry A 2021 Apr 11. Epub 2021 Apr 11.

Key Laboratory of Laser Life Science, Ministry of Education, College of Biophotonics, South China Normal University, Guangzhou, Guangdong, China.

Molecular regulatory network among the B cell leukemia-2 (Bcl-2) family proteins is a research hotspot on apoptosis. The inhibitory priority of anti-apoptotic Bcl-2 family proteins (such as Bcl-xL) to pro-apoptotic Bcl-2 family proteins (such as Bad, tBid and Bax) determines the outcome of their interactions. Based on over-expression model system, we here evaluate the inhibitory priority of Bcl-xL to Bad, tBid and Bax by using live-cell imaging assay on cell viability. Read More

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Licochalcone B Ameliorates Liver Cancer via Targeting of Apoptotic Genes, DNA Repair Systems, and Cell Cycle Control.

Iran J Pharm Res 2020 ;19(4):372-386

Department of Physiology, Faculty of Veterinary Medicine, Kafr El-Sheikh University, Egypt.

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a ubiquitous multifunctional protein required in the DNA base excision repair pathway and a noteworthy reducing-oxidizing factor that regulates the activity of various transcription factors. Cyclin-dependent kinases (CDKs) assume a key role in directing the progression of the cell- cycle. The present study evaluated the synergistic efficacy of using licochalcone B (LCB) and fullerene C (FnC) nanoparticles against diethylnitrosamine (DEN)-induced hepatocarcinoma in rats and relevant signaling pathways, with APE1/Ref-1 and CDK-4, as novel anti-cancer- targeting. Read More

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January 2020

Potentiation of the Anticancer Effects by Combining Docetaxel with Ku-0063794 Against Triple-Negative Breast Cancer Cells.

Cancer Res Treat 2021 Apr 5. Epub 2021 Apr 5.

Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Purpose: mTORC1 and mTORC2 inhibition by Ku-0063794 could confer profound anticancer effects against cancer cells because it eliminates feedback activation of Akt. Herein, we aimed to determine anticancer effects of docetaxel and Ku-0063794, individually or in combination, against breast cancer cells, especially triple negative breast cancer (TNBC) cells.

Material And Methods: MCF-7 breast cancer and MDA-MB-231 TNBC cell lines for in vitro studies and mouse xenograft model for in vivo studies were used to investigate the effect of docetaxel, Ku-0063794, or their combination. Read More

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Resistance to Cell Death in Mucinous Colorectal Cancer-A Review.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.

Mucinous colorectal cancer (CRC) is estimated to occur in approximately 10-15% of CRC cases and is characterized by abundant extracellular mucin. Mucinous CRC is frequently associated with resistance to apoptosis. Inferior prognosis is observed in mucinous CRC, particularly in rectal cancer and metastatic cases. Read More

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Mechanistic Basis for In Vivo Therapeutic Efficacy of CK2 Inhibitor CX-4945 in Acute Myeloid Leukemia.

Cancers (Basel) 2021 Mar 5;13(5). Epub 2021 Mar 5.

Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

Protein Kinase CK2 (Casein Kinase 2 or CK2) is a constitutively active serine-threonine kinase overactive in human malignancies. Increased expression and activity of CK2 in Acute Myeloid Leukemia (AML) is associated with a poor outcome. CK2 promotes AML cell survival by impinging on multiple oncogenic signaling pathways. Read More

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Cardiac Protective Effect of Kirenol against Doxorubicin-Induced Cardiac Hypertrophy in H9c2 Cells through Nrf2 Signaling via PI3K/AKT Pathways.

Int J Mol Sci 2021 Mar 23;22(6). Epub 2021 Mar 23.

Department of Medical Analysis, Al-Hussein Bin Talal University, Ma'an 71111, Jordan.

Kirenol (KRL) is a biologically active substance extracted from Herba Siegesbeckiae. This natural type of diterpenoid has been widely adopted for its important anti-inflammatory and anti-rheumatic properties. Despite several studies claiming the benefits of KRL, its cardiac effects have not yet been clarified. Read More

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Stroma-Mediated Resistance to S63845 and Venetoclax through MCL-1 and BCL-2 Expression Changes Induced by miR-193b-3p and miR-21-5p Dysregulation in Multiple Myeloma.

Cells 2021 Mar 4;10(3). Epub 2021 Mar 4.

Cancer Research Center (IBMCC-CSIC-USAL), University Hospital of Salamanca (IBSAL), 37007 Salamanca, Spain.

BH3-mimetics targeting anti-apoptotic proteins such as MCL-1 (S63845) or BCL-2 (venetoclax) are currently being evaluated as effective therapies for the treatment of multiple myeloma (MM). Interleukin 6, produced by mesenchymal stromal cells (MSCs), has been shown to modify the expression of anti-apoptotic proteins and their interaction with the pro-apoptotic BIM protein in MM cells. In this study, we assess the efficacy of S63845 and venetoclax in MM cells in direct co-culture with MSCs derived from MM patients (pMSCs) to identify additional mechanisms involved in the stroma-induced resistance to these agents. Read More

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