A novel histone deacetylase inhibitor TMU-35435 enhances etoposide cytotoxicity through the proteasomal degradation of DNA-PKcs in triple-negative breast cancer.


:Triple-negative breast cancer (TNBC) treatment offers only limited benefits, and it is very relevant given the significant number of deaths that it causes. DNA repair pathways can enable tumor cells to survive DNA damage that is induced by chemotherapeutic or radiation treatments. Histone deacetylase inhibitors (HDACi) inhibited DNA repair proteins. However, the detailed mechanisms for this inhibition remain unclear. In the present study, we investigated whether a newly developed HDACi, TMU-35435, could enhance etoposide cytotoxicity by inhibiting DNA repair proteins in triple-negative breast cancer. We found synergistic cytotoxicity following treatment of 4T1 cells with etoposide and TMU-35435. Furthermore, TMU-35435 enhances etoposide-induced DNA damage by inhibiting the DNA repair pathway (non-homologous end joining, NHEJ). TMU-35435 suppresses the NHEJ pathway through the ubiquitination of DNA-dependent protein kinase catalytic subunit (DNA-PKcs). In addition, TMU-35435 ubiquitinated DNA-PKcs by inducing the interaction between RNF144A (an E3 ligase) and DNA-PKcs. The combined treatment induced apoptosis and autophagic cell death in 4T1 cells. In an orthotopic breast cancer model, combined treatment with TMU-35435 and etoposide showed anti-tumor growth through the increase of DNA damage and cell death. Taken together, our data suggest that TMU-35435 enhances etoposide cytotoxicity by regulating ubiquitin-proteasome system and inhibiting the DNA repair pathway in TNBC.


Cancer Lett


Cancer letters


Wu YH,Hong CW,Wang YC,Huang WJ,Yeh YL,Wang BJ,Wang YJ,Chiu HW




Has Abstract


2017-08-01 00:00:00












  • Associated nutritional risk of breast and colon cancers: a population-based case-control study in Montreal, Canada.

    abstract::To investigate whether particular patterns of food consumption are related to the occurrence of breast and colon cancer, two simultaneous case-control studies of French-Canadians with 616 cases (414 breast cancer, 202 colon cancer) and 429 population-based controls were carried out. Food consumption data were obtained...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Nkondjock A,Ghadirian P

    更新日期:2005-06-01 00:00:00

  • Nicotine and cotinine in breast fluid.

    abstract::Breast fluid which bathes the mammary ductal epithelium may contain tumorogenic components. In view of the number of tobacco components inhaled during smoking, it was of interest whether nicotine and its metabolites were present in this fluid. Fluid was obtained from the nipple from menstruating women who were smokers...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Hill P,Wynder EL

    更新日期:1979-04-01 00:00:00

  • Bad phosphorylation as a target of inhibition in oncology.

    abstract::Bcl-2 agonist of cell death (BAD) is a BH3-only member of the Bcl-2 family which possesses important regulatory function in apoptosis. BAD has also been shown to possess many non-apoptotic functions closely linked to cancer including regulation of glycolysis, autophagy, cell cycle progression and immune system develop...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Bui NL,Pandey V,Zhu T,Ma L,Basappa,Lobie PE

    更新日期:2018-02-28 00:00:00

  • Induction of cytogenetic adaptive response of mouse bone marrow cells to radiation by therapeutic doses of bleomycin sulfate and actinomycin D as assayed by the micronucleus test.

    abstract::An in vivo micronucleus assay using bone marrow cells of Syrian albino male mice for identifying the possibility of induction of adaptive response to various doses of radiation following treatment with chemotherapeutics is described. Single doses of bleomycin sulfate (BLM-S) at 300 micrograms/kg and actinomycin-D (ACT...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Mozdarani H,Saberi AH

    更新日期:1994-04-01 00:00:00

  • Interstitial and large chromosome 1p deletion occurs in localized and disseminated neuroblastomas and predicts an unfavourable outcome.

    abstract::We studied chromosome 1p loss of heterozygosity (1p-LOH) in 53 neuroblastomas (NBs) using 15 (CA)n repeat loci, which covered a region of 90 cM. We also assessed chromosome 1p36 deletion by fluorescence in situ hybridization (FISH) on interphase nuclei. 1p-LOH was found in 19 (36%, 95% confidence interval (CI) 23-50%)...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Iolascon A,Lo Cunsolo C,Giordani L,Cusano R,Mazzocco K,Boumgartner M,Ghisellini P,Faienza MF,Boni L,De Bernardi B,Conte M,Romeo G,Tonini GP

    更新日期:1998-08-14 00:00:00

  • Synergistic inhibition of human gastric carcinoma cell growth by 1-beta-D-arabinofuranosylcytosine and hydroxyurea or 2'-deoxyguanosine in vitro.

    abstract::The cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in combination with hydroxyurea (HU) or 2'-deoxyguanosine (GdR) on human gastric carcinoma MK-1 cells and colon carcinoma HT-15 cells was studied. Synergistic interaction between ara-C and HU on MK-1 cells and HT-15 cells, or ara-C and GdR on MK-1 cells was...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Matsumoto M,Kawahara T,Tsuda M,Ohkubo T,Kamiguchi H,Yamamura M

    更新日期:1992-04-30 00:00:00

  • Improved chemosensitivity in cervical cancer to cisplatin: synergistic activity of mahanine through STAT3 inhibition.

    abstract::Toxicity reduction of cisplatin is necessary for improved treatment of cancer. Here we have demonstrated the synergistic growth-inhibitory effect of cisplatin on cervical cancer cells in-combination with a nontoxic herbal carbazole alkaloid, mahanine. Mahanine enhanced cisplatin-induced apoptosis and reduced its effec...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Das R,Bhattacharya K,Samanta SK,Pal BC,Mandal C

    更新日期:2014-08-28 00:00:00

  • RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1α mRNA is translated.

    abstract::YTH domain containing 2 (YTHDC2) is a member of the DExD/H-box family of ATP-dependent RNA helicases. We previously found that YTHDC2 expression is up-regulated in several human cancer cells. In this study, we demonstrate novel roles for YTHDC2 in metastasis of colon tumor cells via translation-dependent pathway. Knoc...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Tanabe A,Tanikawa K,Tsunetomi M,Takai K,Ikeda H,Konno J,Torigoe T,Maeda H,Kutomi G,Okita K,Mori M,Sahara H

    更新日期:2016-06-28 00:00:00

  • A synthetic chalcone, 2'-hydroxy-2,3,5'-trimethoxychalcone triggers unfolded protein response-mediated apoptosis in breast cancer cells.

    abstract::The primary aim of this study was to find novel chemopreventive agents effective against breast cancer. Endoplasmic reticulum (ER) stress can induce apoptosis through the unfolded protein response (UPR). 2'-Hydroxy-2,3,5'-trimethoxychalcone (DK143) is a synthetic flavonoid derivative. The present study provides eviden...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Lee DH,Jung Jung Y,Koh D,Lim Y,Lee YH,Shin SY

    更新日期:2016-03-01 00:00:00

  • DNA fragmentation by 2-nitropropane in rat tissues, and effects of the modulation of biotransformation processes.

    abstract::The occurrence and persistence of DNA fragmentation, as detected by the alkaline elution technique, have been studied in rats treated with single oral doses of the hepatocarcinogen 2-nitropropane (2-NP). A progressive increase of liver DNA fragmentation was observed at doses ranging from 0.5 to 8 mmol/kg; single stran...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Robbiano L,Mattioli F,Brambilla G

    更新日期:1991-04-01 00:00:00

  • Cedrol suppresses glioblastoma progression by triggering DNA damage and blocking nuclear translocation of the androgen receptor.

    abstract::Glioblastoma (GBM) is the most common and aggressive primary brain tumor with great invasiveness and resistance to chemotherapy, which presents a treatment challenge. In this study, we investigated the antitumor effect of Cedrol, a sesquiterpene alcohol isolated from Cedrus atlantica, against GBM cells in vitro and in...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Chang KF,Huang XF,Chang JT,Huang YC,Weng JC,Tsai NM

    更新日期:2020-12-28 00:00:00

  • JNK signaling contributes to skeletal muscle wasting and protein turnover in pancreatic cancer cachexia.

    abstract::Cancer cachexia patients experience significant muscle wasting, which impairs the quality of life and treatment efficacy for patients. Skeletal muscle protein turnover is imparted by increased expression of ubiquitin-proteasome pathway components. Mitogen-activated protein kinases p38 and ERK have been shown to augmen...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Mulder SE,Dasgupta A,King RJ,Abrego J,Attri KS,Murthy D,Shukla SK,Singh PK

    更新日期:2020-10-28 00:00:00

  • Cytokine-induced killer cells interact with tumor lysate-pulsed dendritic cells via CCR5 signaling.

    abstract::The antitumor activity of cytokine-induced killer (CIK) cells can be increased by co-culturing them with tumor lysate-pulsed dendritic cells (tDCs); this phenomenon has been studied mainly at the population level. Using time-lapse imaging, we examined how CIK cells gather information from tDCs at the single-cell level...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Lee HK,Kim YG,Kim JS,Park EJ,Kim B,Park KH,Kang JS,Hong JT,Kim Y,Han SB

    更新日期:2016-08-10 00:00:00

  • Intestinal epithelial cells contain a high molecular weight protease subject to inhibition by anticarcinogenic protease inhibitors.

    abstract::Protease inhibitors have been shown to be highly effective suppressors of carcinogenesis in both in vivo and in vitro model systems. For example, the soybean derived Bowman Birk inhibitor (BBI) has been shown to inhibit colon carcinogenesis. Although the precise mechanisms by which protease inhibitors suppress carcino...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Habres JM,Billings PC

    更新日期:1992-04-15 00:00:00

  • Aryl hydrocarbon hydroxylase induction in mitogen-stimulated lymphocytes by benzanthracene or cigarette tars adsorbed to asbestos fibers.

    abstract::Human mitogen-stimulated lymphocytes, cultured in the presence of amosite asbestos (AS), demonstrated a slight increase in aryl hydrocarbon hydroxylase (AHH) activity compared with non-induced (control) cultures (P = 0.005). A much greater increase in enzyme activity occurred following addition of the inducers benzant...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: McLemore TL,Jenkins WT,Arnott MS,Wray NP

    更新日期:1979-07-01 00:00:00

  • p53 protein expression in patients with hepatocellular carcinoma from the high incidence area of Guangxi, Southern China.

    abstract::Mutation of the p53 gene has been reported in hepatocellular carcinoma (HCC) occurring worldwide. The most frequent p53 mutation has been found in HCCs in regions with high hepatitis B virus (HBV) infection and intake of aflatoxin B1 (AFB1). The aim of our study was to examine p53 protein expression in HCCs from a hig...

    journal_title:Cancer letters

    pub_type: 临床试验,杂志文章


    authors: Qin G,Su J,Ning Y,Duan X,Luo D,Lotlikar PD

    更新日期:1997-12-23 00:00:00

  • Tumor exposed-lymphatic endothelial cells promote primary tumor growth via IL6.

    abstract::Solid tumors are composed of tumor cells and stromal cells including lymphatic endothelial cells (LEC), which are mainly viewed as cells forming lymphatic vessels involved in the transport of metastatic and immune cells. We here reveal a new mechanism by which tumor exposed-LEC (teLEC) exert mitogenic effects on tumor...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Van de Velde M,Ebroin M,Durré T,Joiret M,Gillot L,Blacher S,Geris L,Kridelka F,Noel A

    更新日期:2021-01-28 00:00:00

  • Synergistic activity of purine metabolism inhibitors in cultured human tumor cells.

    abstract::Cytotoxic effects of 3-deazaguanosine (3-DGUO) result from the inhibition of DNA synthesis and incorporation of the drug into DNA. Synergistic antiproliferative effects of a combination of 3-deazaguanosine and 2-beta-D-ribofuranosylthiazole-4-carboxamide, a potent inhibitor of inosine monophosphate dehydrogenase, was ...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Jacobsen SJ,Page T,Diala ES,Nyhan WL,Robins RK,Mangum JH

    更新日期:1987-04-01 00:00:00

  • Volatilization of mutagens from beef during cooking.

    abstract::The process of cooking beef substances which are mutagenic in the Ames Salmonella/microsome bioassay [1,2]. In this study, the formation and disposition of basic mutagens produced by cooking beef at different temperatures were examined. Mutagenic activity increased exponentially with cooking temperature between 137 de...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Rappaport SM,McCartney MC,Wei ET

    更新日期:1979-12-01 00:00:00

  • Studies on the kinetics of expression of cell cycle dependent proto-oncogenes during mitogen-induced liver cell proliferation.

    abstract::The present study was undertaken to determine the kinetics of DNA synthesis and expression of cell cycle dependent proto-oncogenes in response to two types of cell proliferative stimuli in male Wistar rat liver. The peak of DNA synthesis was approximately 24 h after a compensatory cell proliferative stimulus induced b...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Coni P,Bignone FA,Pichiri G,Ledda-Columbano GM,Columbano A,Rao PM,Rajalakshmi S,Sarma DS

    更新日期:1989-09-15 00:00:00

  • Blood autoantibodies against tumor-associated antigens as biomarkers in early detection of colorectal cancer.

    abstract::Multiple studies have shown that cancer patients produce detectable autoantibodies against certain tumor-associated antigens, which might be promising blood biomarkers for early detection of colorectal cancer (CRC). We aimed to provide an overview of published studies on blood autoantibody markers for early detection ...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Chen H,Werner S,Tao S,Zörnig I,Brenner H

    更新日期:2014-05-01 00:00:00

  • Feedback loop between p66(Shc) and Nrf2 promotes lung cancer progression.

    abstract::p66(Shc), one of the SHC1 gene encoding proteins, promotes cell death and reports cell anchorage status, mediating anoikis in vitro and functioning as a metastasis suppressor in vivo. However, very little is known about p66(Shc) gene regulation in cancer cells. Here, we show that methylation of a specific CpG site in ...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Du W,Jiang Y,Zheng Z,Zhang Z,Chen N,Ma Z,Yao Z,Terada L,Liu Z

    更新日期:2013-08-28 00:00:00

  • Interferon (IFN)-beta induces apoptotic cell death in DHL-4 diffuse large B cell lymphoma cells through tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

    abstract::The effect of interferon (IFN)-alpha, beta and gamma on the growth of DHL-4 diffuse large B cell lymphoma cells was studied. IFN-beta significantly inhibited the cell growth, and the effect was stronger than that of IFN-alpha. IFN-gamma did not inhibit the cell growth because of lack of IFN-gamma receptors. IFN-beta c...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Oehadian A,Koide N,Mu MM,Hassan F,Islam S,Yoshida T,Yokochi T

    更新日期:2005-07-08 00:00:00

  • Biomimetic models to examine microenvironmental regulation of glioblastoma stem cells.

    abstract::Glioblastoma multiforme (GBM), a malignant brain tumor, is the deadliest form of human cancer with low survival rates because of its highly invasive nature. In recent years, there has been a growing appreciation for the role that glioblastoma stem cells (GSCs) play during tumorigenesis and tumor recurrence of GBM. GSC...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Nakod PS,Kim Y,Rao SS

    更新日期:2018-08-10 00:00:00

  • Magnetic polyethyleneimine (PEI) microcapsules as retrievable traps for carcinogen electrophiles formed in the gastrointestinal tract.

    abstract::Semi-permeable magnetic microcapsules containing polyethyleneimine (PEI) have been developed as retrievable carcinogen traps. In vitro, the soluble core PEI and membrane both bound reactive substances of limited aqueous stability, such as from [14C]N-methyl-N-nitrosourea ([14C]NMU), and aqueous stable dyes of molecula...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Povey AC,Bartsch H,O'Neill IK

    更新日期:1987-07-01 00:00:00

  • Transcriptionally active non-ligand binding oestrogen receptors in breast cancer.

    abstract::Data were obtained on soluble oestrogen (ER) and progesterone (PR) receptors from 273 primary breast tumours, using an enzyme immunoassay (EIA) and ligand binding assay with dextran-coated charcoal (DCC) or isoelectric focussing separations. The p29 and total cathepsin D content was also assayed in the same samples. T...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Marsigliante S,Greco S,Biscozzo L,Barker S,Baker V,Giuseppe L,Vinson GP,Storelli C

    更新日期:1992-10-21 00:00:00

  • Bone marrow-derived fibrocytes promote stem cell-like properties of lung cancer cells.

    abstract::Cancer stem cells (CSCs) represent a minor population that have clonal tumor initiation and self-renewal capacity and are responsible for tumor initiation, metastasis, and therapeutic resistance. CSCs reside in niches, which are composed of diverse types of stromal cells and extracellular matrix components. These stro...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Saijo A,Goto H,Nakano M,Mitsuhashi A,Aono Y,Hanibuchi M,Ogawa H,Uehara H,Kondo K,Nishioka Y

    更新日期:2018-05-01 00:00:00

  • Pre-microRNA variants predict HPV16-positive tumors and survival in patients with squamous cell carcinoma of the oropharynx.

    abstract::To identify non-tumor biomarkers for prediction of tumor HPV status and prognosis of patients with squamous cell carcinoma of the oropharynx (SCCOP), we evaluated the association of single nucleotide polymorphisms (SNPs) in pre-miRNAs with HPV16 status and survival for SCCOP patients. We analyzed HPV16 status in tumor...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Guan X,Sturgis EM,Song X,Liu Z,El-Naggar AK,Wei Q,Li G

    更新日期:2013-04-28 00:00:00

  • Targeted therapy for hepatocellular carcinoma: Challenges and opportunities.

    abstract::Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, which ranks as the sixth of cancer-related death. Despite the emergence of targeted therapy, advanced-stage HCC remains largely incurable due to low response rate and therapeutic resistance. In this review, we mainly focused on the current pro...

    journal_title:Cancer letters

    pub_type: 杂志文章,评审


    authors: Chen S,Cao Q,Wen W,Wang H

    更新日期:2019-09-28 00:00:00

  • A comparison of adrenergic receptors of rat ascites hepatoma AH130 cells with those of normal rat hepatocytes.

    abstract::The pharmacological specificity of adrenergic receptors in the plasma membrane of rat ascites hepatoma AH130 cells was compared with that in normal rat hepatocytes. The number of [125I]iodocyanopindolol-binding sites was much greater in AH130 cells than in the hepatocytes. We characterized the alpha-adrenergic recepto...

    journal_title:Cancer letters

    pub_type: 杂志文章


    authors: Sanae F,Miyamoto K,Koshiura R

    更新日期:1988-04-01 00:00:00