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 Therjournal_title
Cancer biology & therapyauthors
Gang BP,Dilda PJ,Hogg PJ,Blackburn ACdoi
10.4161/15384047.2014.955992subject
Has Abstractpub_date
2014-01-01 00:00:00pages
1533-41issue
11eissn
1538-4047issn
1555-8576journal_volume
15pub_type
杂志文章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
更新日期:2008-04-01 00:00:00
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
更新日期:2015-01-01 00:00:00
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
更新日期:2011-10-15 00:00:00
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:
更新日期:2003-07-01 00:00:00
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
更新日期:2015-01-01 00:00:00
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
更新日期:2014-10-01 00:00:00
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
更新日期:2008-10-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972183
更新日期:2014-01-01 00:00:00
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
更新日期:2006-06-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1046650
更新日期:2015-01-01 00:00:00
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
更新日期:2009-02-01 00:00:00
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
更新日期:2010-08-01 00:00:00
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
更新日期:2011-08-01 00:00:00
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
更新日期:2004-10-01 00:00:00
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
更新日期:2020-09-01 00:00:00
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
更新日期:2014-01-01 00:00:00
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
更新日期:2010-07-01 00:00:00
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
更新日期:2009-04-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.21115
更新日期:2012-09-01 00:00:00
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
更新日期:2019-01-01 00:00:00
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
更新日期:2014-08-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.26044
更新日期:2013-11-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.4.17174
更新日期:2011-08-15 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.11.3302
更新日期:2006-11-01 00:00:00
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
更新日期:2015-01-01 00:00:00
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
更新日期:2011-04-15 00:00:00
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
更新日期:2017-10-03 00:00:00
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
更新日期:2006-08-01 00:00:00
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
更新日期:2005-06-01 00:00:00
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
更新日期:2010-08-01 00:00:00