Anti-leukemic effect of sodium metaarsenite (KML001) in acute myeloid leukemia with breaking-down the resistance of cytosine arabinoside.

Abstract:

:Sodium metaarsenite (NaAs2O3: code name KML001) is an orally bioavailable arsenic compound with potential anti-cancer activity. However, the effect of KML001 has not been studied in acute myeloid leukemia (AML). We investigated the anti-leukemic effect of KML001 in AML, and determined the mode of action of KML001. KML001 inhibited the cellular proliferation in all AML cell lines and primary AML blasts as well as HL-60R (cytosine arabinoside-resistant HL-60) cells, while As2O3 was not effective in primary AML blasts and AML cell lines including HL-60R cells. KML001 induced G1 arrest and apoptosis in HL-60 and HL-60R cells. KML001 inhibited the activation of STAT (signal transducer and activator of transcription) 1, 3, 5, NF-κB, AKT and PI3K, while phosphorylated PTEN was upregulated. In addition, activation of ERK, p38 and JNK was observed in KML001-induced growth inhibition of HL-60 and HL-60R cells. Furthermore, KML001 induced telomeric terminal restriction fragment (TRF) length shortening in a time-dependent manner in HL-60 and HL-60R cells. Real‑time PCR with RNA extracted from KML001-treated HL-60 and HL-60R cells showed a significant reduction of catalytic subunit of telomerase, hTERT, in a time-dependent manner. Additionally, γ-H2AX, a sensitive molecular marker of DNA damage, in HL-60 and HL-60R cells was induced by KML001. These results suggest that KML001 inhibits the proliferation of AML cells including cytosine arabinoside-resistant AML cells via various mechanisms such as cell cycle arrest, induction of apoptosis, inhibition of JAK/STAT and PI3K pathways, activation of MAPK pathway and telomere targeting.

journal_name

Int J Oncol

authors

Yoon JS,Kim ES,Park BB,Choi JH,Won YW,Kim S,Lee YY

doi

10.3892/ijo.2015.2899

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

1953-62

issue

5

eissn

1019-6439

issn

1791-2423

journal_volume

46

pub_type

杂志文章
  • Aldehyde dehydrogenase high gastric cancer stem cells are resistant to chemotherapy.

    abstract::Cancer stem cells (CSCs) are known to influence chemoresistance, survival, relapse and metastasis. Aldehyde dehydrogenase (ALDH) functions as an epithelial CSC marker. In the present study, we investigated the involvement of ALDH in gastric CSC maintenance, chemoresistance and survival. Following screening for eight c...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2013.1837

    authors: Nishikawa S,Konno M,Hamabe A,Hasegawa S,Kano Y,Ohta K,Fukusumi T,Sakai D,Kudo T,Haraguchi N,Satoh T,Takiguchi S,Mori M,Doki Y,Ishii H

    更新日期:2013-04-01 00:00:00

  • CD87-positive tumor cells in bone marrow aspirates identified by confocal laser scanning fluorescence microscopy.

    abstract::Dissemination of single tumor cells to the bone marrow is a common event in cancer. The clinical significance of cytokeratin-positive cells detected in the bone marrow of cancer patients is still a matter of debate. In gastric cancer, overexpression of the receptor (uPAR or CD87) for the serine protease urokinase-type...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.15.4.617

    authors: Noack F,Helmecke D,Rosenberg R,Thorban S,Nekarda H,Fink U,Lewald J,Stich M,Schutze K,Harbeck N,Magdolen V,Graeff H,Schmitt M

    更新日期:1999-10-01 00:00:00

  • Identification by a Digital Gene Expression Displayer (DGED) and test by RT-PCR analysis of new mRNA candidate markers for colorectal cancer in peripheral blood.

    abstract::Evidence from the literature widely supports the efficacy of screening for colorectal cancer (CRC) in reducing mortality. A blood-based assay, potentially, represents a more accessible early detection tool for the identification of circulating tumour cells originating from a primary tumour site in the body. The presen...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000701

    authors: Lauriola M,Ugolini G,Rosati G,Zanotti S,Montroni I,Manaresi A,Zattoni D,Rivetti S,Mattei G,Coppola D,Strippoli P,Taffurelli M,Solmi R

    更新日期:2010-08-01 00:00:00

  • Outcome-based profiling of astrocytic tumours identifies prognostic gene expression signatures which link molecular and morphology-based pathology.

    abstract::Astrocytomas are intracranial malignancies for which invasive growth and high motility of tumour cells preclude total resection; the tumours usually recur in a more aggressive and, eventually, lethal form. Clinical outcome is highly variable and the accuracy of morphology-based prognostic statements is limited. In ord...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Beetz C,Bergner S,Brodoehl S,Brodhun M,Ewald C,Kalff R,Krüger J,Patt S,Kiehntopf M,Deufel T

    更新日期:2006-11-01 00:00:00

  • Clinicopathological and biological significance of CDC28 protein kinase regulatory subunit 2 overexpression in human gastric cancer.

    abstract::CDC28 protein kinase regulatory subunit 2 (CKS2) is a cyclin-dependent kinase subunit (CKS) family member that participates in cell cycle regulation. Few studies have investigated its involvement in gastric cancer. In this study, we focused on the clinical and biological significance of CKS2 over-expression in gastric...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2011.1056

    authors: Tanaka F,Matsuzaki S,Mimori K,Kita Y,Inoue H,Mori M

    更新日期:2011-08-01 00:00:00

  • Expression of cell-associated isoform of vascular endothelial growth factor 189 and its prognostic relevance in non-small cell lung cancer.

    abstract::Vascular endothelial growth factor (VEGF) has four isoforms (VEGF121, VEGF165, VEGF189, VEGF206). We examined the expression patterns of VEGF isoforms in non-small cell lung cancer (NSCLC) by RT-PCR. The cell-associated isoform VEGF189 was more frequently expressed in NSCLC (90.5%) than in extraneoplastic lung tissue ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.12.3.541

    authors: Oshika Y,Nakamura M,Tokunaga T,Ozeki Y,Fukushima Y,Hatanaka H,Abe Y,Yamazaki H,Kijima H,Tamaoki N,Ueyama Y

    更新日期:1998-03-01 00:00:00

  • A dynamic interplay between alternative polyadenylation and microRNA regulation: implications for cancer (Review).

    abstract::Alternative polyadenylation and microRNA regulation are both mechanisms of post-transcriptional regulation of gene expression. Alternative polyadenylation often results in mRNA isoforms with the same coding sequence but different lengths of 3' UTRs, while microRNAs regulate gene expression by binding to specific mRNA ...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:10.3892/ijo.2013.2047

    authors: An J,Zhu X,Wang H,Jin X

    更新日期:2013-10-01 00:00:00

  • Differential expression of hsp90, gelsolin and gst-pi in human gastric-carcinoma cell-lines.

    abstract::We have analyzed proteins produced in Various human gastric carcinoma cell lines and normal gastric mucosa. The production of HSP90 increased in eight gastric carcinoma cell lines. Gelsolin content was down-regulated in seven gastric carcinoma cell lines. Furthermore, the production of GST-pi increased in a poorly dif...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.5.6.1347

    authors: Moriya S,Yanagihara K,Fujita H,Kuzumaki N

    更新日期:1994-12-01 00:00:00

  • COX-2 silencing enhances tamoxifen antitumor activity in breast cancer in vivo and in vitro.

    abstract::Tamoxifen (Tam), a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. However, extended TAM administration for breast cancer induces increased VEGF levels in patients, promoting new blood vessel formation and thereby limiting its efficacy and highlighting ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2299

    authors: Du Y,Shi A,Han B,Li S,Wu D,Jia H,Zheng C,Ren L,Fan Z

    更新日期:2014-04-01 00:00:00

  • The expression of MHC class I, TAP1/2, and LMP2/7 gene in human gastric cancer cell lines.

    abstract::Intracellular antigens are presented to CD8+ T cells through major histocompatibility complex (MHC) class I molecule. For stable MHC class I expression, several molecules as well as the MHC molecule itself have to express simultaneously and function well. To determine a gene associated with MHC class I surface express...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.16.6.1159

    authors: Kang JK,Yoon SJ,Kim NK,Heo DS

    更新日期:2000-06-01 00:00:00

  • Anticancer activity and computational modeling of ternary copper (II) complexes with 3-indolecarboxylic acid and 1,10-phenanthroline.

    abstract::Metal-containing compounds have been extensively studied for many years as potent proteasome inhibitors. The 20S proteasome, the main component of the ubiquitin proteasome pathway, is one of the excellent targets in anticancer drug development. We recently reported that several copper complexes were able to inhibit ca...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2016.3542

    authors: Zhang Z,Wang H,Wang Q,Yan M,Wang H,Bi C,Sun S,Fan Y

    更新日期:2016-08-01 00:00:00

  • Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer.

    abstract::Aurora kinase A (AURKA) regulates the cell cycle checkpoint and maintains genomic integrity. AURKA is overexpressed in various malignant tumors and its upregulation induces chromosomal instability, which leads to aneuploidy and cell transformation. To investigate the role of AURKA in endometrial cancer, we evaluated t...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2015.2842

    authors: Umene K,Yanokura M,Banno K,Irie H,Adachi M,Iida M,Nakamura K,Nogami Y,Masuda K,Kobayashi Y,Tominaga E,Aoki D

    更新日期:2015-04-01 00:00:00

  • Clinical significance of E-cadherin and vimentin co-expression in breast cancer.

    abstract::We examined the clinical significance of E-cadherin and vimentin expression in 83 patients with breast dancer. E-cadherin expression was correlated with axillary metastases, histologic grade, recurrence and disease-free survival, but not with overall survival. On the other hand, vimentin expression was correlated with...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.9.4.755

    authors: Yagasaki R,Noguchi M,Minami M,Earashi M

    更新日期:1996-10-01 00:00:00

  • Thymidine phosphorylase-mediated angiogenesis regulated by thymidine phosphorylase inhibitor in human ovarian cancer cells in vivo.

    abstract::Metastasis or progression of ovarian cancer cells is known to be due to the action of various angiogenic factors. We determined the expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD-ECGF) and vascular endothelial growth factor (VEGF) in cell lines established from 3 serous ad...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Tsukagoshi S,Saga Y,Suzuki N,Fujioka A,Nakagawa F,Fukushima M,Suzuki M

    更新日期:2003-05-01 00:00:00

  • Effects of linoleic-Acid on mammary-tumor cell-proliferation are associated with changes in p53 protein expression.

    abstract::A rat mammary tumor cell line maintained in low serum (1%) medium exhibited a slower growth rate, altered cell cycle distribution, decreased DNA synthesis, and increased immunoprecipitable p53, when compared with culture in 10% serum. Addition of linoleic acid (LA; 18:2, n-6) to low serum medium partially restored nor...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.3.1.81

    authors: Tillotson J,Darzynkiewicz Z,Cohen L,Ronai Z

    更新日期:1993-07-01 00:00:00

  • Increased level of cell-derived microparticles in the cyst fluids of odontogenic keratocysts.

    abstract::The aim of this study was to examine the level and basic characteristics of cell‑derived microparticles (MPs) in the cyst fluids of odontogenic keratocysts (OKCs). For this purpose, MPs from the cyst fluids (CFMPs) of OKCs were purified by a classic differential centrifugation method and characterized by a transmissio...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2018.4361

    authors: Man QW,Zhong WQ,Ren JG,Liu JY,Zheng YY,Li RF,Nyimi BF,Chen G,Zhao YF,Liu B

    更新日期:2018-06-01 00:00:00

  • HIF1-positive and HIF1-negative glioblastoma cells compete in vitro but cooperate in tumor growth in vivo.

    abstract::Glioblastoma multiforme (GBM) is characterized by extensive angiogenesis that is mostly orchestrated by the hypoxia inducible factor HIF-1. Deregulation of HIF-1 is believed to contribute to cancer initiation and progression. However, instances have been described in which loss of HIF-1 leads to more aggressive tumors...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000554

    authors: Fiorenzo P,Mongiardi MP,Dimitri D,Cozzolino M,Ferri A,Montano N,Trevisi G,Maira G,Battistini L,Falchetti ML,Levi A,Pallini R

    更新日期:2010-04-01 00:00:00

  • Preclinical investigation of folate receptor-targeted nanoparticles for photodynamic therapy of malignant pleural mesothelioma.

    abstract::Photodynamic therapy (PDT) following lung-sparing extended pleurectomy for malignant pleural mesothelioma (MPM) has been investigated as a potential means to kill residual microscopic cells. High expression levels of folate receptor 1 (FOLR1) have been reported in MPM; therefore, targeting FOLR1 has been considered a ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2018.4555

    authors: Kato T,Jin CS,Lee D,Ujiie H,Fujino K,Hu HP,Wada H,Wu L,Chen J,Weersink RA,Kanno H,Hatanaka Y,Hatanaka KC,Kaga K,Matsui Y,Matsuno Y,De Perrot M,Wilson BC,Zheng G,Yasufuku K

    更新日期:2018-11-01 00:00:00

  • Androgen-independent prostate cancer cells circumvent EGFR inhibition by overexpression of alternative HER receptors and ligands.

    abstract::The deregulation of the epidermal growth factor receptor (EGFR) pathway plays a major role in the pathogenesis of prostate cancer (PCa). However, therapies targeting EGFR have demonstrated limited effectiveness in PCa. A potential mechanism to overcome EGFR blockade in cancer cells is the autocrine activation of alter...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1509

    authors: Carrión-Salip D,Panosa C,Menendez JA,Puig T,Oliveras G,Pandiella A,De Llorens R,Massaguer A

    更新日期:2012-09-01 00:00:00

  • Injection of irradiated b16 melanoma genetically-modified to secrete IFN-alpha causes regression of an established tumor.

    abstract::Highly aggressive murine B16 melanoma was engineered to secrete IFN-alpha constitutively. Cells expressing IFN-alpha were injected into syngeneic C57BL/6 mice and the mice were monitored for tumor development. Secretion of IFN-alpha by B16 melanoma cells completely abrogated their tumorigenicity in syngeneic mice. LFN...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.7.1.17

    authors: Sarkar S,Flores I,Ron Y,Derosa C,Ozzello L,Pestka S

    更新日期:1995-07-01 00:00:00

  • Vanadium induces AP-1- and NFkappB-dependent transcription activity.

    abstract::Vanadate has been reported to be involved in the causation of cancer. In this study, we found that both AP-1 and NFkappaB activities were increased after treatment with sodium vanadate in JB6 cells. Maximum induction of AP-1 and NFkappaB appeared at 48 to 72 h. Phosphorylations of Erks and p38 kinases were markedly in...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.13.4.711

    authors: Huang C,Chen N,Ma WY,Dong Z

    更新日期:1998-10-01 00:00:00

  • Comparison of telomerase activity in normal chorionic villi to trophoblastic diseases.

    abstract::Trophoblasts are derived from the normal placenta, and they infiltrate into the endometrium and the maternal blood vessels under strict control but, unlike malignant cells, never metastasize. To understand the proliferative characteristics of trophoblasts and its related disorders, we assessed telomerase activity in c...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.12.1.81

    authors: Nishi H,Yahata N,Ohyashiki K,Isaka K,Shiraishi K,Ohyashiki JH,Toyama K,Takayama M

    更新日期:1998-01-01 00:00:00

  • Sorafenib and TRAIL have synergistic effect on hepatocellular carcinoma.

    abstract::A multi-kinase inhibitor, sorafenib, was recently approved and is currently recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, HCC treatment outcomes are still poor and necessitate improvement. Therefore, we investigated the influence of sorafenib in ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1676

    authors: Nojiri K,Sugimoto K,Shiraki K,Tameda M,Inagaki Y,Ogura S,Kasai C,Kusagawa S,Yoneda M,Yamamoto N,Takei Y,Nobori T,Ito M

    更新日期:2013-01-01 00:00:00

  • MAP kinase pathways involved in glioblastoma response to erucylphosphocholine.

    abstract::Erucylphosphocholine (ErPC) is a promising antineoplastic drug for the treatment of malignant brain tumors. It exerts strong anticancer activity and induces apoptosis even in chemoresistant glioma cells. In the present study, A172 and U373MG glioma cells were treated with ErPC to explore the contribution of MAP kinase...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Kugler W,Erdlenbruch B,Otten K,Jendrossek V,Eibl H,Lakomek M

    更新日期:2004-12-01 00:00:00

  • Soy isoflavone genistein modulates cell cycle progression and induces apoptosis in HER-2/neu oncogene expressing human breast epithelial cells.

    abstract::In the multistep progressive pathogenesis of human breast cancer, comedo ductal carcinoma in situ (DCIS) represents a preinvasive precursor lesion for therapy resistant invasive cancer. Human tissue derived cell culture models exhibiting molecular similarities to clinical DCIS facilitate an important preclinical mecha...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Katdare M,Osborne M,Telang NT

    更新日期:2002-10-01 00:00:00

  • ADAM17-siRNA inhibits MCF-7 breast cancer through EGFR-PI3K-AKT activation.

    abstract::A disintegrin and metalloproteinase-17 (ADAM17) can cut and release a wide variety of epidermal growth factor receptor (EGFR) ligands to promote survival, invasion and proliferation of cancer cell, and therefore, is considered to be a potential therapeutic target for cancer. The main goal of the present study was to o...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2016.3536

    authors: Meng X,Hu B,Hossain MM,Chen G,Sun Y,Zhang X

    更新日期:2016-08-01 00:00:00

  • Reliability of a primary culture system to test cytotoxic drug activity in human-malignant melanoma.

    abstract::Optimal conditions have been defined to grow primary cultures of malignant melanoma suitable for in vitro pharmacological studies. A feasibility of primary cultures was observed in 60% of 62 clinical melanoma lymph node metastases. The neoplastic nature of the cells grown in culture, as assessed by the highly specific...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.1.6.619

    authors: Villa R,Zaffaroni N,Orlandi L,Costa A,Veronese S,Vaglini M,Silvestrini R

    更新日期:1992-11-01 00:00:00

  • Importance of immune monitoring approaches and the use of immune checkpoints for the treatment of diffuse intrinsic pontine glioma: From bench to clinic and vice versa (Review).

    abstract::On the basis of immunological results, it is not in doubt that the immune system is able to recognize and eliminate transformed cells. A plethora of studies have investigated the immune system of patients with cancer and how it is prone to immunosuppression, due in part to the decrease in lymphocyte proliferation and ...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:10.3892/ijo.2018.4283

    authors: Scutti JAB

    更新日期:2018-04-01 00:00:00

  • Association between different levels of lipid metabolism‑related enzymes and fatty acid synthase in Wilms' tumor.

    abstract::Wilms' tumor is one of the most common malignant tumors of the abdomen in children. However, there is currently no recognized specific biomarker for the clinical diagnosis and prognosis of this tumor. Lipid metabolism is involved in membrane synthesis and oxidation in tumor cells. This process plays an important role ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2019.4948

    authors: Wang X,Du G,Wu Y,Zhang Y,Guo F,Liu W,Wu R

    更新日期:2020-02-01 00:00:00

  • Expression of cyclin D1 proto-oncogene mRNA in primary meningiomas may contribute to tumorigenesis.

    abstract::Meningiomas are benign brain tumors thought to arise by multi-step tumorigenesis, involving both the activation of oncogenes and the loss of tumor suppressor genes. The cell cycle regulator proto-oncogene cyclin D1 has been implicated in the pathogenesis of several types of cancer. Northern blot analysis revealed expr...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.9.6.1213

    authors: Maxwell M,Galanopoulos T,Antoniades H

    更新日期:1996-12-01 00:00:00