4,592 results match your criteria mcl-1 protein

Promotive effects of HOXA10 antisense RNA on the stemness of oral squamous cell carcinoma stem cells through a microRNA-29a/MCL-1/phosphatidyl inositol 3-kinase/protein kinase B axis.

Dongying Wang

Arch Oral Biol 2021 Mar 31;126:105114. Epub 2021 Mar 31.

Department of Stomatology, Affiliated Hospital of Inner Mongolia University for Nationalities, No.1742, Huolinhe Street, Tongliao, 028000, Inner Mongolia, PR China. Electronic address:

Objective: The aim of this study was to investigate the effects of long non-coding RNA (lncRNA) HOXA10 antisense RNA (HOXA10-AS) on the properties of oral squamous cell carcinoma (OSCC) stem cells and the molecular mechanism.

Design: Tumor and the paracancerous tissues were collected from 83 patients with OSCC. OSCC stem cells were extracted from a human OSCC cell line Tca8113. Read More

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Tubulin acetylation enhances lung cancer resistance to paclitaxel-induced cell death through Mcl-1 stabilization.

Cell Death Discov 2021 Apr 6;7(1):67. Epub 2021 Apr 6.

Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals Research Cluster, Chulalongkorn University, Bangkok, 10330, Thailand.

The posttranslational modifications (PTMs) of microtubules have been reported to play an important role in cancer aggressiveness, including apoptosis resistance. In this study, we aimed to investigate the biological role of microtubule PTMs in the regulation of paclitaxel responsiveness. The acetylated tubulin (Ace-tub) level was strongly associated with paclitaxel sensitivity, as observed in patient-derived primary lung cancer cells and xenografted immunodeficient mice. Read More

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GSK-3: a multifaceted player in acute leukemias.

Leukemia 2021 Apr 2. Epub 2021 Apr 2.

Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.

Glycogen synthase kinase 3 (GSK-3) consists of two isoforms (α and β) that were originally linked to glucose metabolism regulation. However, GSK-3 is also involved in several signaling pathways controlling many different key functions in healthy cells. GSK-3 is a unique kinase in that its isoforms are constitutively active, while they are inactivated mainly through phosphorylation at Ser residues by a variety of upstream kinases. Read More

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High ROS Production by Celecoxib and Enhanced Sensitivity for Death Ligand-Induced Apoptosis in Cutaneous SCC Cell Lines.

Int J Mol Sci 2021 Mar 31;22(7). Epub 2021 Mar 31.

Department of Dermatology, Venerology and Allergology, Skin Cancer Center, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.

Incidence of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis has increased worldwide, and non-steroidal anti-inflammatory drugs as celecoxib are considered for treatment. We show here strong anti-proliferative effects of celecoxib in four cSCC cell lines, while apoptosis and cell viability largely remained unaffected. Impeded apoptosis was overcome in combinations with agonistic CD95 antibody or TNF-related apoptosis-inducing ligand (TRAIL), resulting in up to 60% apoptosis and almost complete loss of cell viability. 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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Downregulation of Mcl-1 by Panobinostat Potentiates Proton Beam Therapy in Hepatocellular Carcinoma Cells.

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

Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, Korea.

Epigenetic modulation by histone deacetylase (HDAC) inhibitors is an attractive anti-cancer strategy for diverse hematological and solid cancers. Herein, we explored the relative effectiveness of the pan-HDAC inhibitor panobinostat in combination with proton over X-ray irradiation in HCC cells. Clonogenic survival assays revealed that radiosensitization of Huh7 and Hep3B cells by panobinostat was more evident when combined with protons than X-rays. Read More

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Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives.

Cancers (Basel) 2021 Mar 14;13(6). Epub 2021 Mar 14.

Research Institute of Medical & Health Sciences, University of Sharjah, P.O. Box 27272 Sharjah, United Arab Emirates.

The major form of cell death in normal as well as malignant cells is apoptosis, which is a programmed process highly regulated by the BCL-2 family of proteins. This includes the antiapoptotic proteins (BCL-2, BCL-XL, MCL-1, BCLW, and BFL-1) and the proapoptotic proteins, which can be divided into two groups: the effectors (BAX, BAK, and BOK) and the BH3-only proteins (BIM, BAD, NOXA, PUMA, BID, BIK, HRK). Notably, the BCL-2 antiapoptotic proteins are often overexpressed in malignant cells. Read More

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Design, Synthesis, and Structural Characterization of Lysine Covalent BH3 Peptides Targeting Mcl-1.

J Med Chem 2021 Apr 2. Epub 2021 Apr 2.

Division of Biomedical Sciences, School of Medicine, University of California Riverside, 900 University Avenue, Riverside, California 92521, United States.

Modulating disease-relevant protein-protein interactions (PPIs) using pharmacological tools is a critical step toward the design of novel therapeutic strategies. Over the years, however, targeting PPIs has proven a very challenging task owing to the large interfacial areas. Our recent efforts identified possible novel routes for the design of potent and selective inhibitors of PPIs using a structure-based design of covalent inhibitors targeting Lys residues. Read More

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Gab1 in livers with persistent hepatocyte apoptosis has an antiapoptotic effect and reduces chronic liver injury, fibrosis and tumorigenesis.

Am J Physiol Gastrointest Liver Physiol 2021 Mar 31. Epub 2021 Mar 31.

Graduate school of Medicine, Department of Gastroenterology and Hepatology, Osaka University, Japan.

Grb2-associated binder 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction by receptor tyrosine kinases that are receptors for various growth factors and plays an important role in rapid liver regeneration after partial hepatectomy and during acute hepatitis. On the other hand, mild liver regeneration is induced in livers of individuals with chronic hepatitis, where hepatocyte apoptosis is persistent; however, the impact of Gab1 on such livers remains unclear. We examined the role of Gab1 in chronic hepatitis. Read More

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Synergistic efficacy of dual PI3K-d/g inhibitor Duvelisib with Bcl2 inhibitor Venetoclax in Richter's Syndrome PDX models.

Blood 2021 Mar 30. Epub 2021 Mar 30.

University of Torino, Torino, Italy.

A small subset of cases of chronic lymphocytic leukemia undergoes transformation to diffuse large B-cell lymphoma, Richter's Syndrome (RS), which is associated with a poor prognosis. Conventional chemotherapy results in limited responses, underlining the need for novel therapeutic strategies. Here, we investigate the ex-vivo and in vivo efficacy of the dual PI3K-d/g inhibitor Duvelisib (Duv) and the Bcl-2 inhibitor Venetoclax (Ven) using four different RS-patient-derived xenograft (PDX) models. Read More

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Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting.

Sci Adv 2021 03 26;7(13). Epub 2021 Mar 26.

VIB Center for Inflammation Research, 9052 Ghent, Belgium.

The therapeutic scope of antibody and nonantibody protein scaffolds is still prohibitively limited against intracellular drug targets. Here, we demonstrate that the Alphabody scaffold can be engineered into a cell-penetrating protein antagonist against induced myeloid leukemia cell differentiation protein MCL-1, an intracellular target in cancer, by grafting the critical B-cell lymphoma 2 homology 3 helix of MCL-1 onto the Alphabody and tagging the scaffold's termini with designed cell-penetration polypeptides. Introduction of an albumin-binding moiety extended the serum half-life of the engineered Alphabody to therapeutically relevant levels, and administration thereof in mouse tumor xenografts based on myeloma cell lines reduced tumor burden. Read More

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Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways.

Eur Rev Med Pharmacol Sci 2021 Mar;25(5):2206-2220

School of Life Sciences, Manipal Academy of Higher Education, Dubai, UAE.

Objective: Chrysin, one of the main active constituents of flavonoids, is known for demonstrating protective effects against various types of cancer including cervical cancer. The aim of this study was to determine apoptosis induction and antiproliferative action of chrysin on human cervical cancer cells.

Materials And Methods: In this study, attempts have been made to establish anticancer role of chrysin on HeLa cells. Read More

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Tea polyphenol EGCG inhibited colorectal-cancer-cell proliferation and migration via downregulation of STAT3.

Gastroenterol Rep (Oxf) 2021 Jan 3;9(1):59-70. Epub 2020 Dec 3.

Key Laboratory, People's Hospital of Longhua, Shenzhen, Guangdong, P. R. China.

Background: Green tea is a popular beverage worldwide and epigallocatechin-3-gallate (EGCG) is the most bioactive polyphenol in green tea. Our study aims to investigate the anti-proliferation and anti-migration effects of EGCG against colorectal-cancer SW480, SW620, and LS411N cells, and elucidate the underlying mechanism.

Methods: The anti-proliferation and anti-migration effects of EGCG against colon-cancer cells were evaluated using MTT, scratch-wound-healing, and transwell-migration assays. Read More

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January 2021

Ruxolitinib induces apoptosis of human colorectal cancer cells by downregulating the JAK1/2-STAT1-Mcl-1 axis.

Oncol Lett 2021 May 4;21(5):352. Epub 2021 Mar 4.

College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.

Under pathological conditions, the Janus kinase (JAK)/STAT signaling pathway can regulate the proliferation, differentiation and migration of tumor cells, including colorectal cancer (CRC). CRC is the third major types of cancer among males and the second among females worldwide. In China, CRC is the fifth common cancer among both males and females. Read More

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MCPIP-1 Restricts Inflammation via Promoting Apoptosis of Neutrophils.

Front Immunol 2021 26;12:627922. Epub 2021 Feb 26.

Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University, Krakow, Poland.

Monocyte chemoattractant protein-induced protein-1 (MCPIP-1) is a potent inhibitor of inflammatory response to pathogens. Acting as endonuclease against transcripts of inflammatory cytokines or transcription factors MCPIP-1 can significantly reduce the cytokine storm, thus limiting the tissue damage. As the adequate resolution of inflammation depends also on the efficient clearance of accumulated neutrophils, we focused on the role of MCPIP-1 in apoptosis and retention of neutrophils. Read More

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February 2021

The multi-kinase inhibitor TG02 induces apoptosis and blocks B-cell receptor signaling in chronic lymphocytic leukemia through dual mechanisms of action.

Blood Cancer J 2021 Mar 13;11(3):57. Epub 2021 Mar 13.

Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.

The constitutive activation of B-cell receptor (BCR) signaling, together with the overexpression of the Bcl-2 family anti-apoptotic proteins, represents two hallmarks of chronic lymphocytic leukemia (CLL) that drive leukemia cell proliferation and sustain their survival. TG02 is a small molecule multi-kinase inhibitor that simultaneously targets both of these facets of CLL pathogenesis. First, its inhibition of cyclin-dependent kinase 9 blocked the activation of RNA polymerase II and transcription. Read More

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The combination of C-Myc rearrangement and 1q21 gain is associated with poor prognosis in multiple myeloma.

Ann Hematol 2021 May 8;100(5):1251-1260. Epub 2021 Mar 8.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing, 100730, China.

The prognostic value of chromosomal 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Add-on Myc aberrations may further worsen the outcome. To investigate whether specific genes located at the 1q21 region, such as myeloid cell leukemia 1 (Mcl-1), are involved in NDMM progression, we examined bone marrow cytogenetic abnormalities in 153 patients with NDMM by fluorescence in situ hybridization. Read More

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Pre-therapeutic efficacy of the CDK inhibitor dinaciclib in medulloblastoma cells.

Sci Rep 2021 Mar 8;11(1):5374. Epub 2021 Mar 8.

School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University, Stoke-on-Trent, UK.

Medulloblastoma (MB) is the most common aggressive paediatric brain tumour and, despite the recent progress in the treatments of MB patients, there is still an urgent need of complementary or alternative therapeutic options for MB infants. Cyclin Dependent Kinase inhibitors (CDKi) are at the front-line of novel targeted treatments for multiple cancers and the CDK4/6 specific inhibitor palbociclib has been pre-clinically identified as an effective option for MB cells. Herein, we identified the pan-CDKi dinaciclib as a promising alternative to palbociclib for the suppression of MB cells proliferation. Read More

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Discovery of novel indole-1,2,4-triazole derivatives as tubulin polymerization inhibitors.

Drug Dev Res 2021 Mar 6. Epub 2021 Mar 6.

College of Chemistry and Chemical Engineering, Guangxi Key Laboratory of Polysaccharide Materials and Modifications, Guangxi University for Nationalities, Nanning, China.

A series of novel indole-1,2,4-triazole derivatives have been designed, synthesized, and evaluated as potential tubulin polymerization inhibitors. The top hit 12, bearing the 3,4,5-trimethoxyphenyl moiety, exhibited substantial anti-proliferative activity against HepG2, HeLa, MCF-7, and A549 cells in vitro with IC values of 0.23 ± 0. Read More

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Activation of Interferon Signaling in Chronic Lymphocytic Leukemia Cells Contributes to Apoptosis Resistance via a JAK-Src/STAT3/Mcl-1 Signaling Pathway.

Biomedicines 2021 Feb 13;9(2). Epub 2021 Feb 13.

Centre de Recherche des Cordeliers, INSERM, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Sorbonne Université, Université Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, F-75006 Paris, France.

Besides their antiviral and immunomodulatory functions, type I (α/β) and II (γ) interferons (IFNs) exhibit either beneficial or detrimental effects on tumor progression. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of abnormal CD5 B lymphocytes that escape death. Drug resistance and disease relapse still occur in CLL. Read More

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February 2021

Drimane Derivatives as the First Examples of Covalent BH3 Mimetics that Target MCL-1.

ChemMedChem 2021 Mar 5. Epub 2021 Mar 5.

Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Saclay, Avenue de la terrasse, 91198, Gif-sur-Yvette Cedex, France.

Drimane sesquiterpenoid dialdehydes are natural compounds with antiproliferative properties. Nevertheless, their mode of action has not yet been discovered. Herein, we demonstrate that various drimanes are potent inhibitors of MCL-1 and BCL-xL, two proteins of the BCL-2 family that are overexpressed in various cancers, including lymphoid malignancies. Read More

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Phosphatase PP2A enhances MCL-1 protein half-life in multiple myeloma cells.

Cell Death Dis 2021 Mar 3;12(3):229. Epub 2021 Mar 3.

Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Multiple myeloma (MM), a treatable but incurable malignancy, is characterized by the growth of clonal plasma cells in protective niches in the bone marrow. MM cells depend on expression of BCL-2 family proteins, in particular MCL-1, for survival. The regulation of MCL-1 is complex and cell type-dependent. Read More

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Anti-CD19 mAb Modified Mesoporous Titanium Dioxide as Exclusively Targeting Vector for Efficient B-lymphoblastic Leukemia Therapy.

J Pharm Sci 2021 Feb 25. Epub 2021 Feb 25.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, China. Electronic address:

B lymphoblastic leukemia (B-LL) is a clonal hematopoietic stem cell neoplasm derived from B-cell progenitors, which mainly occurs in children and adolescents and is one of the main causes of death from malignant tumors in this population. The surface marker CD19 is specifically expressed on the membrane of most malignant B-cells, which is widely used as a marker of B-LL antigen-specific immunotherapy. In this study, mesoporous titanium dioxide nanoparticles (MTNs)-based antibody drug delivery system was designed for B-LL treatment. Read More

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February 2021

The application of BH3 mimetics in myeloid leukemias.

Cell Death Dis 2021 Feb 26;12(2):222. Epub 2021 Feb 26.

Paul O'Gorman Leukaemia Research Centre, University of Glasgow, Glasgow, UK.

Execution of the intrinsic apoptotic pathway is controlled by the BCL-2 proteins at the level of the mitochondrial outer membrane (MOM). This family of proteins consists of prosurvival (e.g. Read More

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February 2021

The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer.

Oncogene 2021 Mar 24;40(11):2112-2129. Epub 2021 Feb 24.

School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshir, UK.

Protein ubiquitination is a critical regulator of cellular homeostasis. Aberrations in the addition or removal of ubiquitin can result in the development of cancer and key components of the ubiquitination machinery serve as oncogenes or tumour suppressors. An emerging target in the development of cancer therapeutics are the deubiquitinase (DUB) enzymes that remove ubiquitin from protein substrates. Read More

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Lycorine hydrochloride induces reactive oxygen species-mediated apoptosis via the mitochondrial apoptotic pathway and the JNK signaling pathway in the oral squamous cell carcinoma HSC-3 cell line.

Oncol Lett 2021 Mar 26;21(3):236. Epub 2021 Jan 26.

School of Basic Medicine, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China.

Poor drug efficacy is a prominent cause of oral squamous cell carcinoma (OSCC) treatment failure. Although increased efforts in developing OSCC therapeutic strategies have been achieved in recent decades, the 5-year survival rate of patients with OSCC remains poor and effective drugs to treat OSCC are lacking. The aim of the present study was to investigate the apoptotic effect caused by lycorine hydrochloride (LH) and to identify its mechanism in the OSCC HSC-3 cell line. Read More

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Artesunate inhibits melanoma progression in vitro via suppressing STAT3 signaling pathway.

Pharmacol Rep 2021 Apr 20;73(2):650-663. Epub 2021 Feb 20.

Department of Biostatistics, Faculty of Medicine, Van Yuzuncu Yil University, Van, 65080, Turkey.

Background: Melanoma is a life-threatening cancer characterized with a potentially metastatic tumor of melanocytic origin. Improved methods or novel therapies are urgently needed to eliminate the development of metastases. Artesunate is a semi-synthetic derivative of artemisinin used for trarment of malaria and cancer. Read More

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It's time to die: BH3 mimetics in solid tumors.

Biochim Biophys Acta Mol Cell Res 2021 Apr 15;1868(5):118987. Epub 2021 Feb 15.

Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Frankfurt, Germany. Electronic address:

The removal of cells by apoptosis is an essential process regulating tissue homeostasis. Cancer cells acquire the ability to circumvent apoptosis and survive in an unphysiological tissue context. Thereby, the Bcl-2 protein family plays a key role in the initiation of apoptosis, and overexpression of the anti-apoptotic Bcl-2 proteins is one of the molecular mechanisms protecting cancer cells from apoptosis. Read More

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BH3 profiling identifies ruxolitinib as a promising partner for venetoclax to treat T-cell prolymphocytic leukemia.

Blood 2021 Feb 17. Epub 2021 Feb 17.

Dana-Farber Cancer Institute, Boston, Massachusetts, United States.

Conventional therapies for patients with T-cell prolymphocytic leukemia (T-PLL) such as cytotoxic chemotherapy and alemtuzumab have limited efficacy and considerable toxicity. Several novel agent classes have demonstrated preclinical activity in T-PLL, including inhibitors of the JAK/STAT and TCR pathways, as well as histone deacetylase (HDAC) inhibitors. Recently, the BCL-2 inhibitor venetoclax also showed some clinical activity in T-PLL. Read More

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February 2021