Targeting of two aspects of metabolism in breast cancer treatment.

Abstract:

:Deregulated metabolism is gaining recognition as a hallmark of cancer cells, and is being explored for therapeutic potential. The Warburg effect is a metabolic phenotype that occurs in 90% of tumors, where glycolysis is favored despite the presence of oxygen. Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor that can reverse the Warburg effect. PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid) is a novel anti-mitochondrial agent that targets the adenine nucleotide transporter in mitochondria and is currently in clinical trials for solid tumors. We have investigated the targeting of two aspects of metabolism, using DCA to promote mitochondrial activity combined with PENAO to inhibit mitochondrial activity, in breast and other carcinoma cell lines. PENAO was effective at low uM concentrations in luminal (T-47D) and triple negative (MDA-MB-231) breast cancer cells, in normoxia and hypoxia. The cytotoxicity of PENAO was enhanced by DCA by a mechanism involving increased reactive oxygen species in both T-47D and MDA-MB-231 cells, however further investigations found it did not always involve PDK2 inhibition or reduction of the mitochondrial membrane potential, which are the accepted mechanisms for DCA induction of apoptosis. Nevertheless, DCA sensitized all cancer cell lines tested toward apoptosis of PENAO. DCA and PENAO are both currently in clinical trials and targeting cancer metabolism with these drugs may offer options for difficult to treat cancers.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Gang BP,Dilda PJ,Hogg PJ,Blackburn AC

doi

10.4161/15384047.2014.955992

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

1533-41

issue

11

eissn

1538-4047

issn

1555-8576

journal_volume

15

pub_type

杂志文章
  • Molecular mechanisms underlying selective cytotoxic activity of BZL101, an extract of Scutellaria barbata, towards breast cancer cells.

    abstract::We studied the mechanism of the cytotoxic activity of BZL101, an aqueous extract from the herb Scutellaria barbata D. Don, which is currently in phase II clinical trial in patients with advanced breast cancer. The phase I trial showed favorable toxicity profile and promising efficacy. We report here that BZL101 induce...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.7.4.5535

    authors: Fong S,Shoemaker M,Cadaoas J,Lo A,Liao W,Tagliaferri M,Cohen I,Shtivelman E

    更新日期:2008-04-01 00:00:00

  • Analysis and significance of c-MET expression in adenoid cystic carcinoma of the salivary gland.

    abstract::Adenoid cystic carcinoma (ACC), a rare salivary gland malignancy, is a histogenetic, morphologic, and clinical heterogeneous disease. Extensive efforts have been made to characterize molecular events associated with these tumors, including the identification of prognostic and predictive biomarkers. Increased copy numb...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1030554

    authors: Bell D,Ferrarotto R,Fox MD,Roberts D,Hanna EY,Weber RS,El-Naggar AK

    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

  • Angiogenesis inhibitors: a new class of drugs.

    abstract::Angiogenesis inhibitors belong to a new class of drugs. Many of these drugs are in clinical trials to treat cancer, while others have recently received FDA approval. However, angiogenesis inhibitors operate by different mechanisms than conventional cytotoxic chemotherapies, and require different guidelines for their o...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:

    authors: Folkman J

    更新日期:2003-07-01 00:00:00

  • Microarray expression profiling of dysregulated long non-coding RNAs in triple-negative breast cancer.

    abstract::Triple-negative breast cancer (TNBC) represents a collection of malignant breast tumors that are often aggressive and have an increased risk of metastasis and relapse. Long non-coding RNAs are generally defined as RNA transcripts measuring 200 nucleotides or longer that do not encode for any protein. During the past d...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1040957

    authors: Chen C,Li Z,Yang Y,Xiang T,Song W,Liu S

    更新日期:2015-01-01 00:00:00

  • Dissecting the roles of E1A and E1B in adenoviral replication and RCAd-enhanced RDAd transduction efficacy on tumor cells.

    abstract::Oncolytic viruses have recently received widespread attention for their potential in innovative cancer therapy. Many telomerase promoter-regulated oncolytic adenoviral vectors retain E1A and E1B. However, the functions of E1A and E1B proteins in the oncolytic role of replication-competent adenovirus (RCAd) and RCAd en...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.29842

    authors: Wei F,Wang H,Chen X,Li C,Huang Q

    更新日期:2014-10-01 00:00:00

  • A homologous promoterless K-ras cDNA targeting endogenous K-ras expression inhibits human pancreatic cancer cell growth in vitro and in vivo.

    abstract::It has been reported that the local introduction of a promoter-less DNA containing the complementary DNA (cDNA) sequence of a gene could induce gene-specific silencing in plants. The feasibility of this kind of silencing in human cancer cells is as yet unknown. The current study was designed to investigate the anti-tu...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.7.10.6586

    authors: Ren XY,Liang ZY,Shi XH,Liu TH

    更新日期:2008-10-01 00:00:00

  • DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer.

    abstract::Current treatment modalities for pancreatic carcinoma afford only modest survival benefits. TRAIL, as a potent and specific inducer of apoptosis in cancer cells, would be a promising new treatment option. However, since not all pancreatic cancer cells respond to TRAIL, further improvements and optimizations are still ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/15384047.2014.972183

    authors: Yu R,Albarenque SM,Cool RH,Quax WJ,Mohr A,Zwacka RM

    更新日期:2014-01-01 00:00:00

  • Regulation of Myc function by ARF: checkpoint for Myc-induced oncogenesis.

    abstract::The alterative reading frame (ARF) protein is unique in its capacity to interact with Mdm2 thus facilitating p53-dependent cell cycle arrest and apoptosis. ARF also acts in a p53-independent manner in which it binds to Myc and interferes with transcriptional activation by Myc thereby inhibiting Myc-induced cell prolif...

    journal_title:Cancer biology & therapy

    pub_type: 评论,杂志文章

    doi:10.4161/cbt.5.6.2939

    authors: Sarkar D,Fisher PB

    更新日期:2006-06-01 00:00:00

  • Multiplying therapies and reducing toxicity in metastatic melanoma.

    abstract::Prior to 2011, only 2 systemic treatments were approved for the treatment of melanoma and these had limited efficacy. In the past 4 years, 6 novel agents have received FDA approval. Herein, we will focus on 4 recently published NEJM papers reporting the results of clinical trials, comprising 4 agents targeting the MAP...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1046650

    authors: Massey PR,Prasad V,Figg WD,Fojo T

    更新日期:2015-01-01 00:00:00

  • A prospective comparision of sequential chemoradiation vs concurrent chemoradiation in locally advanced oropharyngeal carcinomas.

    abstract:PURPOSE:Induction chemotherapy has shown to provide consistent benefit for local control in primary treatment of advanced oropharyngeal cancer. The beneficial role of chemoradiation following induction chemotherapy over concurrent chemoradiation has not been evaluated. Present study evaluates the same prospectively. R...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,随机对照试验

    doi:10.4161/cbt.8.3.7484

    authors: Gupta D,Shukla P,Bisht SS,Dhawan A,Pant MC,Bhatt ML,Gupta S,Gupta R,Negi MP

    更新日期:2009-02-01 00:00:00

  • The antitumor efficacy of IL-24 mediated by E1A and E1B triple regulated oncolytic adenovirus.

    abstract:BACKGROUND:IL-24 (interleukin-24) is a promising, multi-functional anti-cancer agent able to selectively induce tumor cell apoptosis while sparing normal cells. Additionally, IL-24 can enhance the immune response to tumors and suppress tumor angiogenesis. In this study, we introduced IL-24 into the oncolytic adenovirus...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.10.3.12308

    authors: Xiao LL,Wu YM,Qian J,Tan Y,Xie GL,Zhang KJ,Wang YG,Jia XY,Liu XY

    更新日期:2010-08-01 00:00:00

  • Cancer-testis gene expression profiling in esophageal squamous cell carcinoma: identification of specific tumor marker and potential targets for immunotherapy.

    abstract::Cancer-testis antigens (CTAs) are often specifically expressed in cancer cells and under normal conditions are only considered to be expressed in the germ line cells and the placenta. CTAs are potential targets for cancer immunotherapy and therefore necessitates their expression profiling. The expression profile of LA...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.3.15949

    authors: Forghanifard MM,Gholamin M,Farshchian M,Moaven O,Memar B,Forghani MN,Dadkhah E,Naseh H,Moghbeli M,Raeisossadati R,Abbaszadegan MR

    更新日期:2011-08-01 00:00:00

  • APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q.

    abstract:INTRODUCTION:Germ-line mutations of the APC gene are associated with familial adenomatous polyposis, and somatic mutations occur frequently in sporadic colorectal cancer. However, to abrogate APC function, both alleles must be inactivated. Recently, it has been demonstrated that epigenetic modification of the APC promo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.3.10.1113

    authors: Arnold CN,Goel A,Niedzwiecki D,Dowell JM,Wasserman L,Compton C,Mayer RJ,Bertagnolli MM,Boland CR

    更新日期:2004-10-01 00:00:00

  • Silencing the intestinal GUCY2C tumor suppressor axis requires APC loss of heterozygosity.

    abstract::Most sporadic colorectal cancer reflects acquired mutations in the adenomatous polyposis coli (APC) tumor suppressor gene, while germline heterozygosity for mutant APC produces the autosomal dominant disorder Familial Adenomatous Polyposis (FAP) with a predisposition to colorectal cancer. In these syndromes, loss of h...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2020.1779005

    authors: Pattison AM,Barton JR,Entezari AA,Zalewski A,Rappaport JA,Snook AE,Waldman SA

    更新日期:2020-09-01 00:00:00

  • Polymorphisms of p53 and MDM2 genes are associated with severe toxicities in patients with non-small cell lung cancer.

    abstract::Adverse events in platinum-based chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) are major challenges. In this study, we investigated the role of the p53 and MDM2 genes in predicting adverse events in NSCLC patients treated with platinum-based chemotherapy. Specifically, we examined the p53 ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/15384047.2014.956599

    authors: Zheng D,Chen Y,Gao C,Wei Y,Cao G,Lu N,Hou Y,Jiang X,Wang J

    更新日期:2014-01-01 00:00:00

  • SU11248 (sunitinib) directly inhibits the activity of mammalian 5'-AMP-activated protein kinase (AMPK).

    abstract::AMPK has been termed the fuel sensor of mammalian cells because it directly responds to the depletion of the fuel molecule ATP. In previous work, we found that AMPK is strongly activated by tumor-like hypoxia and glucose deprivation, independently of the oxygen response system associated with HIF-1. We also observed h...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.10.1.12162

    authors: Laderoute KR,Calaoagan JM,Madrid PB,Klon AE,Ehrlich PJ

    更新日期:2010-07-01 00:00:00

  • Peroxisome proliferator-activated receptor gamma in bladder cancer: a promising therapeutic target.

    abstract::Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated intracellular transcription factors, members of the nuclear hormone receptor superfamily. The PPAR subfamily consist of three subtypes encoded by distinct genes denoted PPARalpha, PPARbeta/delta, and PPARgamma. The peroxisome proliferator-activat...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.8.7.7853

    authors: Mansure JJ,Nassim R,Kassouf W

    更新日期:2009-04-01 00:00:00

  • Increasing the therapeutic index of 5-fluorouracil and 6-thioguanine by targeting loss of MTAP in tumor cells.

    abstract::Methylthioadenosine phosphorylase (MTAP), a key enzyme in the catabolism of 5'-deoxy-5'-methylthioadenosine (MTA), catalyzes the formation of adenine and 5-methylthioribose-1-phosphate. MTAP is expressed in all cells throughout the body, but a significant percentage of human tumors have lost MTAP expression, thereby m...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.21115

    authors: Tang B,Testa JR,Kruger WD

    更新日期:2012-09-01 00:00:00

  • Current state of melanoma diagnosis and treatment.

    abstract::Melanoma is the deadliest form of skin cancer. In the early stages, melanoma can be treated successfully with surgery alone and survival rates are high, but after metastasis survival rates drop significantly. Therefore, early and correct diagnosis is key for ensuring patients have the best possible prognosis. Melanoma...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.1080/15384047.2019.1640032

    authors: Davis LE,Shalin SC,Tackett AJ

    更新日期:2019-01-01 00:00:00

  • Rapamycin enhances cetuximab cytotoxicity by inhibiting mTOR-mediated drug resistance in mesenchymal hepatoma cells.

    abstract::The synergistic effect of combined drug therapy provides an enhanced treatment for advanced liver cancer. We aimed to investigate the underlying mechanism of cetuximab sensitization by rapamycin in hepatoma cells. Four hepatoma cell lines, HepG2, HuH7, SNU-387, and SNU-449, were treated with cetuximab or cetuximab plu...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.29113

    authors: Chen W,Hu QD,Xia XF,Liang C,Liu H,Zhang Q,Ma T,Liang F,Liang TB

    更新日期:2014-08-01 00:00:00

  • Mitogen-activated protein kinase phosphatase-1 inhibition and sustained extracellular signal-regulated kinase 1/2 activation in camptothecin-induced human colon cancer cell death.

    abstract::Camptothecins are commonly used chemotherapeutics; in some models, they enhance signaling via the mitogen-activated protein kinase (MAPK) pathway through effects on upstream kinases. To evaluate the impact of camptothecin (CPT) on MAPKs in human colon cancer, we studied HCT116 and CaCo2 colon cancer cells. We found th...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.26044

    authors: Lee M,Young Kim S,Kim J,Kim HS,Kim SM,Kim EJ

    更新日期:2013-11-01 00:00:00

  • Prediction of proapoptotic anticancer therapeutic response in vivo based on cell death visualization and TRAIL death ligand-receptor interaction.

    abstract::Tumor growth is often associated with insufficient apoptosis. The Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) and its proapoptotic receptors death receptor 4 (DR4) and DR5 agonistic monoclonal antibodies are being developed as targeted therapeutics because they kill cancer cells while sparing...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.4.17174

    authors: Zhou L,Wang W,Dicker DT,Humphreys RC,El-Deiry WS

    更新日期:2011-08-15 00:00:00

  • Furanonaphthoquinones cause apoptosis of cancer cells by inducing the production of reactive oxygen species by the mitochondrial voltage-dependent anion channel.

    abstract::The mitochondrial production of reactive oxygen species has been implicated in the anticancer activity of furanonaphthoquinone. However, the mechanism of the activation remains elusive. In the current study, we found that treatment of HeLa cells with 2-methyl-5(or -8)-hydroxy-furanonaphthoquinone (FNQ13) induces mitoc...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.5.11.3302

    authors: Simamura E,Hirai K,Shimada H,Koyama J,Niwa Y,Shimizu S

    更新日期:2006-11-01 00:00:00

  • Small molecule inhibitors of IRES-mediated translation.

    abstract::Many genes controlling cell proliferation and survival (those most important to cancer biology) are now known to be regulated specifically at the translational (RNA to protein) level. The internal ribosome entry site (IRES) provides a mechanism by which the translational efficiency of an individual or group of mRNAs c...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1071729

    authors: Vaklavas C,Meng Z,Choi H,Grizzle WE,Zinn KR,Blume SW

    更新日期:2015-01-01 00:00:00

  • Wild-type and mutant p53 proteins interact with mitochondrial caspase-3.

    abstract::Caspases play a key role in the apoptotic pathway by virtue of their ability to cleave key protein substrates within the dying cell. Caspases are produced as inactive zymogens, and need to become proteolytically processed in order to become active. A key executioner caspase, caspase-3, has previously been found to exi...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.11.8.14906

    authors: Frank AK,Pietsch EC,Dumont P,Tao J,Murphy ME

    更新日期:2011-04-15 00:00:00

  • Effective treatment of aggressive fibromatosis with celecoxib guided by genetic testing.

    abstract::Aggressive fibromatosis (AF) or desmoid tumors is an aggressive fibroblastic proliferation which is locally invasive but can not metastasize. The treatment of AF is challenging. Surgery was the main treatment modality for AF in the past, other strategies including radiotherapy, systemic therapies and wait-and-see poli...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2017.1373215

    authors: Yang S,Wang X,Jiang H,Wang Y,Li Z,Lu H

    更新日期:2017-10-03 00:00:00

  • A proposed clinical test for monitoring fluoropyrimidine therapy: detection and stability of thymidylate synthase ternary complexes.

    abstract::5-fluorouracil forms classic (covalent, ternary) complexes consisting of thymidylate synthase, fluoro-deoxyuridine monophosphate, and 5,10-methylene tetrahydrofolate. Despite a high pharmacologic interest in the classic complexes formed in cells treated with fluorouracil anticancer agents, the in vivo stability of the...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.5.8.2976

    authors: Brody JR,Gallmeier E,Yoshimura K,Hucl T,Kulesza P,Canto MI,Hruban RH,Schulick RD,Kern SE

    更新日期:2006-08-01 00:00:00

  • Intestinal metaplasia with a high salt diet induces epithelial proliferation and alters cell composition in the gastric mucosa of mice.

    abstract::Intestinal metaplasia of the gastric mucosa is an important component in the pathway to adenocarcinoma. The mechanisms that induce the progression from intestinal metaplasia to cancer have not been elucidated. High dietary salt has been known as one of the risk factors for gastric cancer development in humans. Therefo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.4.6.1734

    authors: Xiao F,Crissey MA,Lynch JP,Kaestner KH,Silberg DG,Suh E

    更新日期:2005-06-01 00:00:00

  • The role of the miR-200 family in epithelial-mesenchymal transition.

    abstract::MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Genes encoding miRNAs are located in regions of the genome that are commonly amplified, deleted or rearranged. They are commonly dysregulated in human cancers and known to act as oncogenes ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.10.3.12548

    authors: Mongroo PS,Rustgi AK

    更新日期:2010-08-01 00:00:00