Functional characterization of NAD dependent de-acetylases SIRT1 and SIRT2 in B-Cell Chronic Lymphocytic Leukemia (CLL).

Abstract:

:Sirtuins (SIRT) are nicotinamide adenine dinucleotide (NAD+) dependent deacetylases or ADP- ribosyl transferases (ARTs) that deacetylate lysine residues on various proteins regulating a variety of cellular and metabolic processes. These enzymes regulate metabolism, cell survival, differentiation and DNA repair. SIRT proteins play an important role in the survival and drug resistance of cancer cells. The purpose of the present study was to investigate the expression and role of SIRT in chronic lymphocytic leukemia (CLL). We analyzed the expression of SIRT1 and SIRT2 in CLL and normal B cells using the Oncomine database as well as by Western blotting of fresh CLL cells from patients and pro-lymphocytic leukemia (PLL) cell lines, JVM-3 and MEC-2. We showed that both primary CLL cells and JVM-3 and MEC-2 cell lines overexpress high levels of functional SIRT1 and SIRT2. SIRT inhibitors EX-527 and sirtinol impair cell growth, induce ROS production, loss of mitochondrial membrane potential and apoptosis in primary CLL cells and cell lines. Using shRNA knock down of SIRT1 and SIRT2 in JVM-3 and MEC-2 cell lines, we showed that expression of both proteins is crucial for the survival of these cells. Furthermore, studies in nutrient deprived conditions suggest a role of SIRT in metabolism in CLL. These results demonstrate that the inhibition of SIRT1 and SIRT2 activity may be a new therapeutic approach for CLL.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Bhalla S,Gordon LI

doi

10.1080/15384047.2016.1139246

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

300-9

issue

3

eissn

1538-4047

issn

1555-8576

journal_volume

17

pub_type

杂志文章
  • Tumor cells and memory T cells converge at glycolysis: therapeutic implications.

    abstract::In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8(+) memory T (Tems) cells glycolyt...

    journal_title:Cancer biology & therapy

    pub_type: 评论,杂志文章

    doi:10.4161/cbt.28160

    authors: Karthikeyan S,Geschwind JF,Ganapathy-Kanniappan S

    更新日期:2014-05-01 00:00:00

  • Polymorphisms of SPINK1 N34S and CFTR in patients with sporadic and familial pancreatic cancer.

    abstract::Long standing chronic pancreatitis is a risk factor for developing pancreatic cancer. Inheritance of polymorphisms in SPINK1 and CFTR are associated with an increased risk of developing pancreatitis. The aim of this study was to determine if patients who carry polymorphisms in SPINK1 and CFTR are at increased risk of ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:

    authors: Matsubayashi H,Fukushima N,Sato N,Brune K,Canto M,Yeo CJ,Hruban RH,Kern SE,Goggins M

    更新日期:2003-11-01 00:00:00

  • Indoleamine 2,3-dioxygenase (IDO) expression in lung cancer.

    abstract:BACKGROUND:The expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells has been considered as a major tumor immune escape mechanism. The aim of this study was to investigate the expression of IDO in lung cancer cell lines as well as in surgically resected lung cancer specimens comparing the latter, to the expres...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.8.4446

    authors: Karanikas V,Zamanakou M,Kerenidi T,Dahabreh J,Hevas A,Nakou M,Gourgoulianis KI,Germenis AE

    更新日期:2007-08-01 00:00:00

  • Chetomin, a Hsp90/HIF1α pathway inhibitor, effectively targets lung cancer stem cells and non-stem cells.

    abstract::Non-small cell lung cancer (NSCLC) remains recalcitrant to effective treatment due to tumor relapse and acquired resistance. Cancer stem cells (CSCs) are believed to be one mechanism for relapse and resistance and are consequently considered promising drug targets. We report that chetomin, an active component of Chaet...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2020.1763147

    authors: Min S,Wang X,Du Q,Gong H,Yang Y,Wang T,Wu N,Liu X,Li W,Zhao C,Shen Y,Chen Y,Wang X

    更新日期:2020-08-02 00:00:00

  • Combined endostatin and TRAIL gene transfer suppresses human hepatocellular carcinoma growth and angiogenesis in nude mice.

    abstract::Endostatin can inhibit tumor growth by blocking angiogenesis, whereas tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may function as a soluble cytokine to selectively kill cancer cells without toxicity to most normal cells. To establish the combined anti-tumor therapeutic effect of endostatin and solu...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.8.5.7687

    authors: Zhang Y,Qu ZH,Cui M,Guo C,Zhang XM,Ma CH,Sun WS

    更新日期:2009-03-01 00:00:00

  • Human prostate cancer ZIP1/zinc/citrate genetic/metabolic relationship in the TRAMP prostate cancer animal model.

    abstract::Prostate cancer is the second leading cause of cancer deaths among men. The availability of animal models that represent the events and factors that exist in the natural history and biology of human prostate cancer is essential in dealing with prostate cancer. In recent decades and presently, emphasis has been directe...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.12.18367

    authors: Costello LC,Franklin RB,Zou J,Feng P,Bok R,Swanson MG,Kurhanewicz J

    更新日期:2011-12-15 00:00:00

  • MicroRNA-23a depletion promotes apoptosis of ovarian cancer stem cell and inhibits cell migration by targeting DLG2.

    abstract::Ovarian cancer (OC) is xenogeneic that is influenced by many generated factors related to epigenetic factors to accelerate tumor metastasis. This study was conducted with the objective of investigating the effect of microRNA-23a-3p (miR-23a) on the biological characteristics of OC stem cells by targeting discs large h...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2019.1579960

    authors: Zhuang RJ,Bai XX,Liu W

    更新日期:2019-01-01 00:00:00

  • The molecular pathogenesis of head and neck cancer.

    abstract::Head and neck cancer arises from a series of molecular alterations progressive from dysplasia to carcinoma in situ, and finally invasive carcinoma. Risk factors associated with head and neck cancer include tobacco, alcohol and viral infection. There are genetic alterations in pre-cancerous cells that contribute to tra...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.9.1.10905

    authors: Klein JD,Grandis JR

    更新日期:2010-01-01 00:00:00

  • Systemic and skin toxicity in Cercopithecus aethiops sabaeus monkeys treated during 26 weeks with a high intravenous dose of the anti- epidermal growth factor receptor monoclonal antibody Nimotuzumab.

    abstract::Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor monoclonal antibody (mAb) registered for treating head and neck tumours. The present study was designed to evaluate the systemic and skin toxicity of chronic intravenous administration of the h-R3 in a relevant species demonstrated by comparing th...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.9.4539

    authors: Arteaga ME,Ledón N,Casacó A,Pardo B,García M,Boleda M,Viña L,Orphee R,Hernández O,González C,Fuentes D,Rodríguez V,Charro L,Baro F,Macías A,Pérez A,Morales Y,Subirós N,González B,Ramos M,Rodriquez L,Ballester-La

    更新日期:2007-09-01 00:00:00

  • HIF prolyl hydroxylase-2 inhibition diminishes tumor growth through matrix metalloproteinase-induced TGFβ activation.

    abstract::A right amount of oxygen and nutrients is essential for a tumor to develop. The role of oxygen dependent pathways and their regulators is therefore of utmost importance although little is known about the detailed impact they can have. Recently we have shown that inhibition of the oxygen sensor PHD2 in tumor cells bloc...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.13.4.18830

    authors: Klotzsche-von Ameln A,Muschter A,Heimesaat MM,Breier G,Wielockx B

    更新日期:2012-02-15 00:00:00

  • Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy.

    abstract::We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1026507

    authors: Wyluda EJ,Cheng J,Schell TD,Haley JS,Mallon C,Neves RI,Robertson G,Sivik J,Mackley H,Talamo G,Drabick JJ

    更新日期:2015-01-01 00:00:00

  • Detection of apoptotic circulating tumor cells in advanced pancreatic cancer following 5-fluorouracil chemotherapy.

    abstract::The objective of the present study was to evaluate CA19-9 and CK8/18 expression patterns in pancreatic cancer cell lines induced by 5-fluorouracil (5-Fu), and in circulating tumor cells (CTCs) in peripheral blood of patients previously untreated with advanced pancreatic cancer. Furthermore, the goal was to test the re...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.8.15960

    authors: Ren C,Han C,Zhang J,He P,Wang D,Wang B,Zhao P,Zhao X

    更新日期:2011-10-15 00:00:00

  • Growth inhibitory effects of gastric cancer cells with an increase in S phase and alkaline phosphatase activity repression by aloe-emodin.

    abstract::Aloe-emodin is a novel active compound found in the root and rhizome of Rheum palmatum. To investigate the effects and mechanisms of aloe-emodin on human gastric cancer, MGC-803 cells were treated with 2.5, 5, 10, 20 and 40 microM aloe-emodin for 1-5 d. The results showed that aloe-emodin inhibited the growth of cance...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.1.3553

    authors: Guo J,Xiao B,Zhang S,Liu D,Liao Y,Sun Q

    更新日期:2007-01-01 00:00:00

  • A targeted IL-15 fusion protein with potent anti-tumor activity.

    abstract::IL-15 has been actively investigated for its potential in tumor immunotherapy. To enhance the anti-tumor activity of IL-15, the novel PFC-1 construct was designed, which comprises the following 3 parts: (1) IL-15Rα fused with IL-15 to enhance IL-15 activity, (2) an Fc fragment to increase protein half-life, and (3) an...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1071739

    authors: Chen S,Huang Q,Liu J,Xing J,Zhang N,Liu Y,Wang Z,Li Q

    更新日期:2015-01-01 00:00:00

  • The status of zinc in the development of hepatocellular cancer: an important, but neglected, clinically established relationship.

    abstract::Liver cancer (hepatocellular carcinoma, HCC) is increasing worldwide. About 75% of HCC cases result in death generally within one year. The factors responsible for the initiation and progression of HCC remain largely unknown and speculative, thereby impeding advancements in the development of effective therapeutic age...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.27633

    authors: Costello LC,Franklin RB

    更新日期:2014-04-01 00:00:00

  • Adenovirus-mediated Ink4a/ARF gene transfer significantly suppressed the growth of pancreatic carcinoma cells.

    abstract:OBJECTIVES:To determine the effects of adenovirus-mediated transfer of p14(ARF) and p16(INK4a) on growth and apoptosis of human pancreatic carcinoma cell lines. RESULTS:Pancreatic carcinoma cell lines, PC-7, PANC-1 and MIA PaCa-2 (p14(ARF)-/- and p16(INK4a)-/-), were used. PC-7 (p53 wt) and MIA PaCa-2 (p53 mt) cells i...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.4.12.2183

    authors: Chen F,Li Y,Lu Z,Gao J,Chen J

    更新日期:2005-12-01 00:00:00

  • Chimeric cytokine receptor enhancing PSMA-CAR-T cell-mediated prostate cancer regression.

    abstract::Objective: Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated an unprecedented therapeutic efficacy in hematological malignancies; however, its effectiveness in solid tumors remains elusive. In order to enable CAR-T cells more effective to solid tumors, a inverted chimeric cytokine receptor (ICR) was de...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2020.1739952

    authors: Weimin S,Abula A,Qianghong D,Wenguang W

    更新日期:2020-06-02 00:00:00

  • Upregulation of the androgen receptor during prostate cancer progression.

    abstract::The androgen receptor is one of the central factors in mediating prostate cancer progression and is an important target for treatment. Several possible mechanisms have been put forth as to how it promotes this process. In the January 2004 issue of Nature Medicine, Chen et al. report that the androgen receptor is consi...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.3.3.785

    authors: Singh A,Figg WD

    更新日期:2004-03-01 00:00:00

  • Connectivity map identifies HDAC inhibition as a treatment option of high-risk hepatoblastoma.

    abstract::Hepatoblastoma (HB) is the most common liver tumor of childhood, usually occurring in children under the age of 3 y. The prognosis of patients presenting with distant metastasis, vascular invasion and advanced tumor stages remains poor and children that do survive often face severe late effects from the aggressive che...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2016.1235664

    authors: Beck A,Eberherr C,Hagemann M,Cairo S,Häberle B,Vokuhl C,von Schweinitz D,Kappler R

    更新日期:2016-11-01 00:00:00

  • Apoptotic response to 5-fluorouracil treatment is mediated by reduced polyamines, non-autocrine Fas ligand and induced tumor necrosis factor receptor 2.

    abstract::5-fluorouracil (5-FU) is the major chemotherapeutic agent for treatment of colorectal carcinoma, but the molecular mechanisms of response and resistance are not understood completely. We therefore studied the 5-FU dose response and time course of gene expression transcriptome changes in colon carcinoma cell lines that...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.2.5.532

    authors: Zhang W,Ramdas L,Shen W,Song SW,Hu L,Hamilton SR

    更新日期:2003-09-01 00:00:00

  • Increased gene copy number of the transcription factor E2F1 in malignant melanoma.

    abstract::Translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process. We have previously shown a unique translocation in malignant melanoma cells der(12)t(12;20). The transcription factor E2F1 maps to 20q11. Increased expression of E2F h...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.5.4.2512

    authors: Nelson MA,Reynolds SH,Rao UN,Goulet AC,Feng Y,Beas A,Honchak B,Averill J,Lowry DT,Senft JR,Jefferson AM,Johnson RC,Sargent LM

    更新日期:2006-04-01 00:00:00

  • mDia function is critical for the cell suicide program triggered by farnesyl transferase inhibition.

    abstract::Farnesyl transferase inhibitors (FTIs) exhibit limited cytotoxic effects against human cancer cells, perhaps explaining the limited efficacy of FTIs in clinical trials. Learning how these well-tolerated drugs trigger p53-independent apoptosis in mouse models of cancer might therefore benefit efforts to leverage their ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.9.4546

    authors: Kamasani U,Duhadaway JB,Alberts AS,Prendergast GC

    更新日期:2007-09-01 00:00:00

  • Cost-effectiveness of RAS screening before monoclonal antibodies therapy in metastatic colorectal cancer based on FIRE3 Study.

    abstract::The surprising results published by FIRE-3 revealed that the overall survival (OS) of RAS wild-type metastatic colorectal cancer (mCRC) patients treated with Cetuximab(Cmab) and FOLFIRI combination was prolonged to 33.1 months. The substantial increase in testing and treatment costs, however, impose a considerable hea...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1095398

    authors: Wen F,Yang Y,Zhang P,Zhang J,Zhou J,Tang R,Chen H,Zheng H,Fu P,Li Q

    更新日期:2015-01-01 00:00:00

  • Binding and inhibition of drug transport proteins by heparin: a potential drug transporter modulator capable of reducing multidrug resistance in human cancer cells.

    abstract::A major problem in cancer treatment is the development of resistance to chemotherapeutic agents, multidrug resistance (MDR), associated with increased activity of transmembrane drug transporter proteins which impair cytotoxic treatment by rapidly removing the drugs from the targeted cells. Previously, it has been show...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.27148

    authors: Chen Y,Scully M,Petralia G,Kakkar A

    更新日期:2014-01-01 00:00:00

  • Enhancement of specific cellular immune response induced by glycosyl-phosphatidylinositol-anchored BCR/ABL and mIL-12.

    abstract::bcr/abl fusion gene is thought to be a promising target for chronic myelogenous leukemia (CML) patients to enhance immune response after attaining complete remission. In this study, we sought to enhance cellular immunity by co-expression of BCR/ABL and murine IL-12 gene on the tumor cell surface as a glycosyl-phosphat...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.10.17674

    authors: Tao K,Li YJ,Wang D,Qi JY,Deng YP,Wang HX,Hu J,Feng WL

    更新日期:2011-11-15 00:00:00

  • Drug-induced inactivation or gene silencing of class I histone deacetylases suppresses ovarian cancer cell growth: implications for therapy.

    abstract::There is an urgent need to develop new strategies to treat ovarian cancer, the most deadly gynecologic malignancy. Histone deacetylase (HDAC) inhibitors are emerging as novel therapeutic drugs in the treatment of a variety of cancers, including those resistant to standard chemotherapy. Since there are multiple HDAC is...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.6.5.4007

    authors: Khabele D,Son DS,Parl AK,Goldberg GL,Augenlicht LH,Mariadason JM,Rice VM

    更新日期:2007-05-01 00:00:00

  • CXCL4 mediates tumor regrowth after chemotherapy by suppression of antitumor immunity.

    abstract::The recurrence of colorectal cancer after chemotherapy is the leading cause of its high mortality. We propose that elucidating the mechanisms of tumor regrowth after chemotherapy in tumor-bearing mice may provide new insights into tumor relapse in cancer patients. We firstly report the identification of a chemokine, C...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1095404

    authors: Zhang Y,Gao J,Wang X,Deng S,Ye H,Guan W,Wu M,Zhu S,Yu Y,Han W

    更新日期:2015-01-01 00:00:00

  • Histone deacetylase inhibitors modulate renal cell carcinoma sensitivity to TRAIL/Apo-2L-induced apoptosis by enhancing TRAIL-R2 expression.

    abstract::Every year, 12,000 people in the U.S. die from renal cell carcinoma. Current therapies include partial or complete nephrectomy or treatments such as administration of IFN-alpha and/or interleukins that are moderately effective, at best. Moreover, the current therapies are invasive and inefficient and new therapies are...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.4.10.2022

    authors: VanOosten RL,Moore JM,Karacay B,Griffith TS

    更新日期:2005-10-01 00:00:00

  • Stromal-epithelial interactions are responsible for prostate tumor progression through an androgen-related mechanism.

    abstract::While several hypotheses have been put forward to explain how prostate tumors become resistant to androgen deprivation therapy, the mechanism by which prostate tumors have increased androgen concentrations as compared to the serum has been poorly explored. Using a stromal/epithelial cell co-culture model, Mizokami et ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.9.3.11143

    authors: Sharma H,Sissung TM,Pressler H,Figg WD

    更新日期:2010-02-01 00:00:00

  • Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients.

    abstract:OBJECTIVES:Due to the absence of reliable and accurate biomarkers for the early detection of liver malignancy, circulating microRNAs have recently emerged as great candidates for prompt cancer identification. Therefore, the aim of this study was to investigate the potential of liver-specific circulating microRNAs as an...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2018.1423922

    authors: Mourad L,El-Ahwany E,Zoheiry M,Abu-Taleb H,Hassan M,Ouf A,Rahim AA,Hassanien M,Zada S

    更新日期:2018-05-04 00:00:00