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::Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, are the first targeted therapy drugs approved for the treatment of advanced non-small-cell lung cancer (NSCLC). Interestingly, treatment with these small molecule, reversible EGFR-TKIs leads to more positive respo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.9.8.11881
更新日期:2010-04-15 00:00:00
abstract::The chemotherapeutic agents doxorubicin (dox) or 5-fluorouracil (5FU) are used to treat cancer cells as they cause irreparable DNA damage, inducing these aberrant cells to undergo cell death. The mediator of this process is presumed to be in part the tumor suppressor p53 which regulates genes involved in DNA repair an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.29112
更新日期:2014-08-01 00:00:00
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:
更新日期:2003-11-01 00:00:00
abstract::Tumors with identical phenotype can have markedly different biologic behavior. The differentiation between hemangioblastoma, a benign vascular brain tumor, and renal cell carcinoma (RCC), a malignant tumor that can metastasize to the brain, is a well-known pathological quandary. We report a 59-year-old female with von...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.3.3673
更新日期:2007-03-01 00:00:00
abstract::Current knowledge of changes in the mammary epithelium relevant to breast carcinogenesis is limited to when histological changes are already present because of a lack of biomarkers needed to identify where such molecular changes might be ongoing at earlier during the of decades-long latent stages of breast carcinogene...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.13.2.18873
更新日期:2012-01-15 00:00:00
abstract::We investigated the role of vasculogenic mimicry (VM) in the progression of prostate cancer (PCa). Ninety-six patients who had undergone prostatectomy for treatment of PCa and for whom a complete record of clinical and follow-up data were available were reviewed. VM and matrix metalloproteinase-2 (MMP-2) were detected...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.19602
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND:Peripheral primitive neuroectodermal tumor isolated in the heart, presenting as a primary cardiac tumor is considered as extremely rare. METHODS:We present a 53-year-old Chinese female with a cardiac tumor which was discovered by CT. RESULTS:A hypo-intense tumorous mass was shown extending from the left ve...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1264542
更新日期:2017-01-02 00:00:00
abstract::Aberrant methylation of tumour suppressor genes is associated with the progression to a blast crisis in chronic myeloid leukaemia (CML). Methyl-CpG-binding domain protein 2 (MBD2) has been studied as a "reader" of DNA methylation in many cancers, but its role in CML is unclear. We constructed cell models of a homozygo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1450113
更新日期:2018-08-03 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
abstract::Colon cancer is the third most common cancer and third most common cause of cancer-related death in the USA according to 2008 American Cancer Society statistics. The carcinogenesis of colon cancer has been associated with both genetics and environmental factors. It has been found that several signal pathways, includin...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.8.14.8983
更新日期:2009-07-01 00:00:00
abstract::The colorectal cancer is the leading contributor of cancer-related mortality. Mammalian target of rapamycin (mTOR), existing in 2 complexes (mTORC1/2), is frequently dysregulated and constitutively activated in colorectal cancers. It represents an important drug target. Here we found that INK-128, the novel ATP-compet...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/15384047.2014.972274
更新日期:2015-01-01 00:00:00
abstract::Mortality data by geographic area and trend-based surveillance are particularly relevant in orienting public health decisions targeting specific populations. We analyzed overall and site-specific cancer mortality between 1988 and 2009 in the metropolitan area of Naples and Caserta in southern Italy. Age-standardized m...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.26425
更新日期:2013-12-01 00:00:00
abstract::Cancer cells convert glucose preferentially to lactate even in the presence of oxygen (aerobic glycolysis-Warburg effect). New concepts in cancer treatment aim at inhibition of aerobic glycolysis. Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation. Therefore, the aim of this study ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.22003
更新日期:2012-12-01 00:00:00
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
更新日期:2012-09-01 00:00:00
abstract::We investigated the cytotoxic interactions of romidepsin, a histone deacetylase inhibitor, and lenalidomide, an immunomodulatory agent, in a T-cell lymphoma preclinical model. Hut-78 and Karpas-299 cells were treated with romidepsin and lenalidomide alone and in combination. The interaction between romidepsin and lena...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1219820
更新日期:2016-10-02 00:00:00
abstract::Recently, we showed that the metal chelator TPEN targets colon cancer cells through redox cycling of copper. Here, we studied the DNA damage potential of TPEN and deciphered the role of Chk1, ATM and DNA-PK in TPEN-induced toxicity in 3 human colon cancer cell lines, HCT116, SW480 and HT29. We also investigated the ro...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1235658
更新日期:2016-11-01 00:00:00
abstract:OBJECTIVES:We herein assessed the influence of Epidermal Growth Factor Receptor (EGFR) gene mutations on EGFR expression levels, downstream mediators such as Akt or ERK, and overall survival in patients with ovarian cancer. STUDY DESIGN:EGFR mutation status was analyzed by direct sequencing in 102 Japanese ovarian can...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.1.13877
更新日期:2011-01-01 00:00:00
abstract::KRAS mutational status has been shown to be a predictive biomarker of resistance to anti-EGFR monoclonal antibody (mAb) therapy in patients with metastatic colorectal cancer. We report the spectrum of KRAS mutation in 1506 patients with colorectal cancer and the identification and characterization of rare insertion mu...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.28550
更新日期:2014-06-01 00:00:00
abstract::Chronic myeloid leukemia (CML) progresses from a chronic phase to a deadly blast crisis phase. While it is known that BCR-ABL initiates the disease and that secondary molecular and genetic abnormalities likely contribute to progression of the disease to blast crisis, details regarding the mechanism(s) of blast phase p...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.10.14010
更新日期:2010-11-15 00:00:00
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
更新日期:2007-09-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most deadly tumors. Prognosis of patients with HCC is generally poor due to the high recurrence rate. In the present study, TaqMan Real-time PCR microRNA Array was used to identify differentially expressed miRNAs from 10 tumor tissue samples (5 from recurrence group vs. 5 f...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1071730
更新日期:2015-01-01 00:00:00
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
更新日期:2015-01-01 00:00:00
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
更新日期:2014-01-01 00:00:00
abstract::The clinical use of EGFR-targeted therapy, in triple negative breast cancer patients, has been limited by the development of resistance to these drugs. Although activated signaling molecules contribute to this process, the molecular mechanisms remain relatively unknown. We have previously reported that the small GTPas...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1071737
更新日期:2015-01-01 00:00:00
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
更新日期:2006-11-01 00:00:00
abstract::Colorectal cancer (CRC) is the third most common form of cancer. Current treatments including chemotherapy, radiotherapy and surgery are all associated with a high risk of complications and are not always successful, highlighting the need to develop new treatment strategies. The ingestion of probiotics, prebiotics or ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.10.3296
更新日期:2006-10-01 00:00:00
abstract::Vitamin D derivatives can induce differentiation of human acute myeloid leukemia (AML) cells. Here, we investigated if the G₁ cell cycle block associated with monocytic differentiation is modulated by the p53 status of the cells treated with 1,25D, alone or with plant antioxidants carnosic acid (C) or silibinin (S), a...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.4.12366
更新日期:2010-08-15 00:00:00
abstract::Inflammation is an important factor promoting the progression of glioblastoma. In the present study we examined the contribution of Ras signaling and TNFα/IL-1β cytokines to the development of the glioblastoma inflammatory microenvironment. Enhanced activation of Ras through de-regulated activation of receptor tyrosin...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1139249
更新日期:2016-04-02 00:00:00
abstract::MicroRNAs (miRNAs), an important class of small regulatory molecules for gene expression, are transcribed by RNA polymerase II. But little is known about the mechanisms that control miRNA expression. Comparing miRNA expression profiles between colon cancer cell line HCT 116 and its derivative, DNA methyltransferase 1 ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.8.4486
更新日期:2007-08-01 00:00:00
abstract::Epidemiological studies suggest that obesity increases the risk of developing several cancers, including melanoma. Obesity increases the expression of angiogenic factors, such as leptin, that may contribute to tumor growth. However, a direct cause and effect relationship between obesity and tumor growth has not been c...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.19.9650
更新日期:2009-10-01 00:00:00