90 results match your criteria survivin acetylation

Selinexor versus doxorubicin in dedifferentiated liposarcoma PDXs: evidence of greater activity and apoptotic response dependent on p53 nuclear accumulation and survivin down-regulation.

J Exp Clin Cancer Res 2021 Mar 1;40(1):83. Epub 2021 Mar 1.

Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori, Via Amadeo 42, 20133, Milan, Italy.

Background: Dedifferentiated liposarcoma (DDLPS), a tumor that lacks effective treatment strategies and is associated with poor outcomes, expresses amplified MDM2 in the presence of wild-type p53. MDM2 ubiquitination of p53 facilitates its XPO1-mediated nuclear export, thus limiting p53 tumor suppressor functions. Consequently, nuclear export is a rational target in DDLPS. Read More

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The role of CUDC-907, a dual phosphoinositide-3 kinase and histone deacetylase inhibitor, in inhibiting proliferation of adult T-cell leukemia.

Eur J Haematol 2020 Dec 3;105(6):763-772. Epub 2020 Sep 3.

Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.

Objectives: New effective therapeutic strategies for human T-cell leukemia virus type 1 (HTLV-1)-driven adult T-cell leukemia (ATL) are required because of resistance to chemotherapeutic agents. Here, we aimed to determine the therapeutic efficacy of a dual phosphoinositide 3 kinase (PI3K)/histone deacetylase (HDAC) inhibitor, CUDC-907.

Methods: Cell viability, cell cycle progression, and apoptotic events were examined by WST-8 assay, flow cytometry, and Hoechst 33342 staining. Read More

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December 2020

Tau acetylates and stabilizes β-catenin thereby promoting cell survival.

EMBO Rep 2020 03 13;21(3):e48328. Epub 2020 Jan 13.

Key Laboratory of Ministry of Education of China for Neurological Disorders, Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Overexpressing Tau counteracts apoptosis and increases dephosphorylated β-catenin levels, but the underlying mechanisms are elusive. Here, we show that Tau can directly and robustly acetylate β-catenin at K49 in a concentration-, time-, and pH-dependent manner. β-catenin K49 acetylation inhibits its phosphorylation and its ubiquitination-associated proteolysis, thus increasing β-catenin protein levels. Read More

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Overexpression of microRNA-203 can downregulate survivin and function as a potential therapeutic target in papillary thyroid cancer.

Oncol Lett 2020 Jan 13;19(1):61-68. Epub 2019 Nov 13.

Department of Thyroid Surgery, Ningbo No. 2 Hospital, Ningbo Medical University, Ningbo, Zhejiang 315010, P.R. China.

Papillary thyroid cancer (PTC) is the most common type of thyroid carcinoma. PTC has a considerably high five-year survival rate; however, the possibility of recurrence is also high. Therefore, there is a requirement to clarify the molecular mechanism of PTC to promote understanding regarding the development of the disease and further improve prognosis. Read More

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January 2020

Lovastatin-mediated MCF-7 cancer cell death involves LKB1-AMPK-p38MAPK-p53-survivin signalling cascade.

J Cell Mol Med 2020 01 10;24(2):1822-1836. Epub 2019 Dec 10.

Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

There is increasing evidence that statins, which are widely used in lowering serum cholesterol and the incidence of cardiovascular diseases, also exhibits anti-tumour properties. The underlying mechanisms by which statins-induced cancer cell death, however, remain incompletely understood. In this study, we explored the anti-tumour mechanisms of a lipophilic statin, lovastatin, in MCF-7 breast cancer cells. Read More

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January 2020

HOXA10 knockdown inhibits proliferation, induces cell cycle arrest and apoptosis in hepatocellular carcinoma cells through HDAC1.

Cancer Manag Res 2019 26;11:7065-7076. Epub 2019 Jul 26.

Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China.

Background: Homeobox A10 (HOXA10) has been implicated in the development and progression of various human cancers. However, the precise biological functions of HOXA10 in hepatocellular carcinoma (HCC) have not been defined.

Methods: In this study, we examined mRNA expression by quantitative real-time PCR (qRT-PCR) of HOXA10 as well as histone deacetylase (HDAC) and protein levels by Western blot of HOXA10, HDAC1, Cyclin D1, proliferating cell nuclear antigen (PCNA), Survivin and p53 acetylation in HCC tissues and cell lines. Read More

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Suppression of STAT3 Phosphorylation and RelA/p65 Acetylation Mediated by MicroRNA134 Plays a Pivotal Role in the Apoptotic Effect of Lambertianic Acid.

Int J Mol Sci 2019 Jun 19;20(12). Epub 2019 Jun 19.

College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.

As p300-mediated RelA/p65 hyperacetylation by signal transducers and activators of transcription 3 (STAT3) is critical for NF-κB activation, in the current study, the apoptotic mechanism of lambertianic acid (LA) was explored in relation to STAT3 phosphorylation and RelA/p65 acetylation in MCF-7, DU145, PC-3, and MDA-MB-453 cells. LA significantly increased the cytotoxicity, sub G 1 population, and the cleavage of poly (ADP-ribose) polymerase (PARP) in MDA-MB-453 or PC-3 cells (STAT3 mutant), more than in the MCF-7 or DU145 cells (STAT3 wild). Consistently, LA inhibited the phosphorylation of STAT3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and disrupted the interaction between p-STAT3, p300, NF-κB, and RelA/p65 acetylation (Ac-RelA/p65) in the MCF-7 and DU145 cells. Read More

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Down-regulation and nuclear localization of survivin by sodium butyrate induces caspase-dependent apoptosis in human oral mucoepidermoid carcinoma.

Oral Oncol 2019 01 5;88:160-167. Epub 2018 Dec 5.

Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea. Electronic address:

Objective: Sodium butyrate (NaBu) is a histone deacetylase inhibitor that possesses an apoptotic ability. However, the molecular mechanism by which NaBu induces apoptosis in human oral mucoepidermoid carcinoma (MEC), a type of salivary gland tumor, remains unclear.

Materials And Methods: The anticancer effects of NaBu and its related molecular mechanisms were determined by trypan blue exclusion assay, 4'-6-diamidino-2-phenylindole staining, live/dead assay, human apoptosis array, RT-PCR, western blotting, immunocytochemistry, preparation of nuclear fractions, and nude mice tumor xenograft. Read More

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January 2019

Comparison of the antifibrotic effects of the pan-histone deacetylase-inhibitor panobinostat versus the IPF-drug pirfenidone in fibroblasts from patients with idiopathic pulmonary fibrosis.

PLoS One 2018 27;13(11):e0207915. Epub 2018 Nov 27.

Department of Internal Medicine, Justus-Liebig-University Giessen, Giessen, Germany.

Background: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a poor prognosis. Pirfenidone is the first antifibrotic agent to be approved for IPF-treatment as it is able to slow down disease progression. However, there is no curative treatment other than lung transplantation. Read More

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Paeonol attenuates isoflurane anesthesia-induced hippocampal neurotoxicity via modulation of JNK/ERK/P38MAPK pathway and regulates histone acetylation in neonatal rat.

J Matern Fetal Neonatal Med 2020 Jan 29;33(1):81-91. Epub 2018 Oct 29.

Department of Neonatology, The Children's Hospital, School of Medicine, Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang Province, China.

Volatile anesthetic such as isoflurane causes widespread neurodegeneration in the developing animal brains and also induces cognitive impairments. Paeonol is a plant-derived phenolic compound possessing numerous bioactive properties. The study investigates the neuroprotective effects of paeonol against isoflurane-induced neurodegeneration and cognitive disturbances in neonatal rats. Read More

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January 2020

A Novel Hydroxamate-Based Compound WMJ-J-09 Causes Head and Neck Squamous Cell Carcinoma Cell Death via LKB1-AMPK-p38MAPK-p63-Survivin Cascade.

Front Pharmacol 2018 1;9:167. Epub 2018 Mar 1.

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Growing evidence shows that hydroxamate-based compounds exhibit broad-spectrum pharmacological properties including anti-tumor activity. However, the precise mechanisms underlying hydroxamate derivative-induced cancer cell death remain incomplete understood. In this study, we explored the anti-tumor mechanisms of a novel aliphatic hydroxamate-based compound, WMJ-J-09, in FaDu head and neck squamous cell carcinoma (HNSCC) cells. Read More

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Nitric oxide antagonism to glioblastoma photodynamic therapy and mitigation thereof by BET bromodomain inhibitor JQ1.

J Biol Chem 2018 04 12;293(14):5345-5359. Epub 2018 Feb 12.

From the Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226-3548

Endogenous nitric oxide (NO) generated by inducible NO synthase (iNOS) promotes glioblastoma cell proliferation and invasion and also plays a key role in glioblastoma resistance to chemotherapy and radiotherapy. Non-ionizing photodynamic therapy (PDT) has anti-tumor advantages over conventional glioblastoma therapies. Our previous studies revealed that glioblastoma U87 cells up-regulate iNOS after a photodynamic challenge and that the resulting NO not only increases resistance to apoptosis but renders surviving cells more proliferative and invasive. Read More

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Epigenetic mechanism of survivin dysregulation in human cancer.

Sci China Life Sci 2018 07 4;61(7):808-814. Epub 2018 Jan 4.

Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.

Survivin (coding gene BIRC5) is a dual functional protein acting as a critical inhibitor of apoptosis (IAP) and key regulator of cell cycle progression. It is usually produced in embryonic tissues during development and undetectable in most adult tissues. Overexpression of Survivin frequently occurs in various human cancers and increased Survivin correlates with poor clinic outcome, tumor recurrence, and therapeutic resistance. Read More

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Combined inhibition of BET proteins and class I HDACs synergistically induces apoptosis in urothelial carcinoma cell lines.

Clin Epigenetics 2018 4;10. Epub 2018 Jan 4.

Department of Urology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany.

Background: New efficient therapies for urothelial carcinoma (UC) are urgently required. Small-molecule drugs targeting chromatin regulators are reasonable candidates because these regulators are frequently mutated or deregulated in UC. Indeed, in previous work, Romidepsin, which targets class I histone deacetylases (HDAC), efficiently killed UC cells, but did not elicit canonical apoptosis and affected benign urothelial cells indiscriminately. Read More

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February 2019

Induction of autophagy and autophagy-dependent apoptosis in diffuse large B-cell lymphoma by a new antimalarial artemisinin derivative, SM1044.

Cancer Med 2018 02 26;7(2):380-396. Epub 2017 Dec 26.

State Key Laboratory for Medical Genomics, Department of Hematology, Shanghai Institute of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. R-CHOP is currently the standard therapy for DLBCL, but the prognosis of refractory or recurrent patients remains poor. In this study, we synthesized a new water-soluble antimalarial drug artemisinin derivative, SM1044. Read More

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February 2018

WMJ-8-B, a novel hydroxamate derivative, induces MDA-MB-231 breast cancer cell death via the SHP-1-STAT3-survivin cascade.

Br J Pharmacol 2017 Sep 1;174(17):2941-2961. Epub 2017 Aug 1.

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Background And Purpose: Histone deacetylase (HDAC) inhibitors have been demonstrate to have broad-spectrum anti-tumour properties and have attracted lots of attention in the field of drug discovery. However, the underlying anti-tumour mechanisms of HDAC inhibitors remain incompletely understood. In this study, we aimed to characterize the underlying mechanisms through which the novel hydroxamate-based HDAC inhibitor, WMJ-8-B, induces the death of MDA-MB-231 breast cancer cells. Read More

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September 2017

SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes.

BMC Dermatol 2017 06 10;17(1). Epub 2017 Jun 10.

School of Medical Science, Edith Cowan University, 270 Joondalup Drive, Joondalup, Perth, WA, 6027, Australia.

Background: Exposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes. Read More

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Nuclear survivin promoted by acetylation is associated with the aggressive phenotype of oral squamous cell carcinoma.

Cell Cycle 2017 May 6;16(9):894-902. Epub 2017 Apr 6.

d Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education , Shanghai Jiao Tong University School of Medicine , Shanghai , China.

Defects in apoptotic pathway contribute to development and progression of oral cancer. Survivin, a member of the inhibitors of apoptosis protein (IAP) family, is increased in many types of cancers. However, it is unclear whether increased survivin is associated with oral squamous cell carcinomas (OSCC), and what mechanisms may involve in. Read More

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Neuroprotective effects of artemisinin against isoflurane-induced cognitive impairments and neuronal cell death involve JNK/ERK1/2 signalling and improved hippocampal histone acetylation in neonatal rats.

J Pharm Pharmacol 2017 Jun 12;69(6):684-697. Epub 2017 Mar 12.

Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Objective: This study was performed to assess the effect of artemisinin against isoflurane-induced neuronal apoptosis and cognitive impairment in neonatal rats.

Methods: Artemisinin (50, 100 or 200 mg/kg b.wt/day; oral gavage) was administered to separate groups of neonatal rats starting from postnatal day 3 (P3) to postnatal day 21 (P21). Read More

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Sirt3-mediated mitophagy protects tumor cells against apoptosis under hypoxia.

Oncotarget 2016 Jul;7(28):43390-43400

Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410008, China.

Sirt3, a mitochondrial deacetylase, participates in the regulation of multiple cellular processes through its effect on protein acetylation. The objective of this study was to explore the role of Sirt3 in the mitochondrial autophagy (mitophagy), a process of the specific autophagic elimination of damaged mitochondria. We found that silencing of Sirt3 expression in human glioma cells by RNA interference blunted the hypoxia-induced the localization of LC3 on the mitochondria, and the degradation of mitochondria. Read More

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Lovastatin causes FaDu hypopharyngeal carcinoma cell death via AMPK-p63-survivin signaling cascade.

Sci Rep 2016 04 28;6:25082. Epub 2016 Apr 28.

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Statins are used widely to lower serum cholesterol and the incidence of cardiovascular diseases. Growing evidence shows that statins also exhibit beneficial effects against cancers. In this study, we investigated the molecular mechanisms involved in lovastatin-induced cell death in Fadu hypopharyngeal carcinoma cells. Read More

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Inhibition of HDAC3- and HDAC6-Promoted Survivin Expression Plays an Important Role in SAHA-Induced Autophagy and Viability Reduction in Breast Cancer Cells.

Front Pharmacol 2016 31;7:81. Epub 2016 Mar 31.

Department of Pharmacology, College of Medicine, National Cheng Kung UniversityTainan, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung UniversityTainan, Taiwan.

SAHA is a class I HDAC/HDAC6 co-inhibitor and an autophagy inducer currently undergoing clinical investigations in breast cancer patients. However, the molecular mechanism of action of SAHA in breast cancer cells remains unclear. In this study, we found that SAHA is equally effective in targeting cells of different breast cancer subtypes and tamoxifen sensitivity. Read More

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The effects of a novel aliphatic-chain hydroxamate derivative WMJ-S-001 in HCT116 colorectal cancer cell death.

Sci Rep 2015 Oct 29;5:15900. Epub 2015 Oct 29.

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Hydroxamate derivatives have attracted considerable attention due to their broad pharmacological properties and have been extensively investigated. We recently demonstrated that WMJ-S-001, a novel aliphatic hydroxamate derivative, exhibits anti-inflammatory and anti-angiogenic activities. In this study, we explored the underlying mechanisms by which WMJ-S-001 induces HCT116 colorectal cancer cell death. Read More

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October 2015

Valproic Acid Induces the Hyperacetylation of P53, Expression of P53 Target Genes, and Markers of the Intrinsic Apoptotic Pathway in Midorganogenesis Murine Limbs.

Birth Defects Res B Dev Reprod Toxicol 2015 Oct 25;104(5):177-83. Epub 2015 Aug 25.

Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

In utero exposure to valproic acid (VPA), an anticonvulsant and histone deacetylase inhibitor (HDACi), increases the risk of congenital malformations. Although the mechanisms leading to the teratogenicity of VPA remain unsolved, several HDAC inhibitors increase cell death in cancer cell lines and embryonic tissues. Moreover, P53, the master regulator of apoptosis, is an established HDAC target. Read More

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October 2015

Histone acetyltransferase p300 is induced by p38MAPK after photodynamic therapy: the therapeutic response is increased by the p300HAT inhibitor anacardic acid.

Free Radic Biol Med 2015 Sep 19;86:118-32. Epub 2015 May 19.

Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan. Electronic address:

Oxidative stress mediated by photodynamic therapy (PDT) mediates the tumoricidal effect, but has also been shown to induce the expression of prosurvival molecules, such as cyclooxygenase-2 (COX-2), which is involved in tumor recurrences after PDT. However, the molecular mechanism is still not fully understood. In this study, we found that activated p38MAPK could significantly up-regulate the activity and expression of histone acetyltransferase p300 (p300HAT) in A375 and C26 cells treated with ALA-and chlorin e6 (Ce6)-mediated photodynamic treatment. Read More

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September 2015

Dual inhibition of HDAC and EGFR signaling with CUDC-101 induces potent suppression of tumor growth and metastasis in anaplastic thyroid cancer.

Oncotarget 2015 Apr;6(11):9073-85

Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies that currently has no effective therapy. We performed quantitative high-throughput screening (qHTS) in three ATC cell lines using 3,282 clinically approved drugs and drug candidates, and identified 100 active agents. Enrichment analysis of active compounds showed that inhibitors of EGFR and histone deacetylase (HDAC) were most active. Read More

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Mitotic activity of survivin is regulated by acetylation at K129.

Cell Cycle 2015 ;14(11):1738-47

a School of Life Sciences; University of Nottingham; Queen's Medical Centre ; Nottingham , UK.

Survivin is a cancer-associated protein regulated by multiple factors, including acetylation at K129 within its C-terminal α-helical tail. Acetylation of survivin is being pursued as a potential prognostic marker in breast cancer. This modification at K129 may cause nuclear accumulation of survivin in interphase cells; however, whether this affects its essential role during mitosis has not been addressed. Read More

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[Antibodies for detection of E/K amino acid substitution in 129 position of the survivin sequence].

Bioorg Khim 2014 Jul-Aug;40(4):443-50

Survivin is an oncofetal protein involved both in inhibiting of apoptosis and in cell cycle regulation. The functions of survivin are defined by its structural state. Due to nature polymorphism, survivin cancontain either E or K amino acid in 129 residue, and K129 is commonly acetylated. Read More

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WMJ-S-001, a novel aliphatic hydroxamate derivative, exhibits anti-angiogenic activities via Src-homology-2-domain-containing protein tyrosine phosphatase 1.

Oncotarget 2015 Jan;6(1):85-100

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Angiogenesis, one of the major routes for tumor invasion and metastasis represents a rational target for therapeutic intervention. Recent development in drug discovery has highlighted the diverse biological and pharmacological properties of hydroxamate derivatives. In this study, we characterized the anti-angiogenic activities of a novel aliphatic hydroxamate, WMJ-S-001, in an effort to develop novel angiogenesis inhibitors. Read More

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January 2015

RPL24: a potential therapeutic target whose depletion or acetylation inhibits polysome assembly and cancer cell growth.

Oncotarget 2014 Jul;5(13):5165-76

Buck Institute for Research on Aging; Novato, CA, USA. Oncology-Hematology Division, Department of Medicine, University of California, San Francisco, CA USA.

Partial loss of large ribosomal subunit protein 24 (RPL24) function is known to protect mice against Akt or Myc-driven cancers, in part via translational inhibition of a subset of cap(eIF4E)-dependently translated mRNAs. The role of RPL24 in human malignancies is unknown. By analyzing a public dataset of matched human breast cancers and normal mammary tissue, we found that breast cancers express significantly more RPL24 than matched normal breast samples. Read More

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