Targeting of two aspects of metabolism in breast cancer treatment.


: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.


Cancer Biol Ther


Cancer biology & therapy


Gang BP,Dilda PJ,Hogg PJ,Blackburn AC




Has Abstract


2014-01-01 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


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

    更新日期:2008-10-01 00:00:00

  • Endometrial cancer with congenital uterine anomalies: 3 case reports and a literature review.

    abstract:BACKGROUND:Uterine malformation is a rare deformity in woman, and only a few cases concerning endometrial cancer arising in patients with congenital uterine anomalies have been reported. Herein, we present 3 cases of endometrial cancer with different congenital uterine anomalies, and review studies involving congenital...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审


    authors: Gao J,Zhang J,Tian W,Teng F,Zhang H,Zhang X,Wang Y,Xue F

    更新日期:2017-03-04 00:00:00

  • Downregulation of XIAP and induction of apoptosis by the synthetic cyclin-dependent kinase inhibitor GW8510 in non-small cell lung cancer cells.

    abstract::Small-molecule inhibitors of cyclin-dependent kinases (CDKs) are known to induce cell cycle arrest and apoptosis in certain cancer cells. In order to evaluate the antitumor activity of one such inhibitor, GW8510, against human lung cancers, we analyzed the effects of GW8510 on six nonsmall cell lung cancer (NSCLC) cel...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Dong F,Guo W,Zhang L,Wu S,Teraishi F,Davis JJ,Fang B

    更新日期:2006-02-01 00:00:00

  • Low density lipoprotein receptor mediates anti-VEGF effect of lymphocyte T-derived microparticles in Lewis lung carcinoma cells.

    abstract::Nonstop proliferation and vigorous neovascularization are two prominent characteristics of cancer. Antiangiogenic therapy has emerged as an important modality in treatment of solid tumors. Our previous work demonstrated that microparticles derived from apoptotic T-lymphocytes (LMPs) not only reduced the viabilities of...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Yang C,Gagnon C,Hou X,Hardy P

    更新日期:2010-09-01 00:00:00

  • Hybrids of aneuploid human cancer cells permit complementation of simple and complex cancer defects.

    abstract::Causes for the complex phenotypes of cancers, such as altered differentiation, invasion and metastasis, are not known, and multigenic defects are likely. In contrast, well-defined deficiencies, such as those affecting DNA-repair mechanisms and enzymatic pathways, are simple, typically caused by one or a few gene mutat...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Dezentje DA,Arking DE,Kortenhorst MS,West K,Chakravarti A,Kern SE

    更新日期:2009-02-01 00:00:00

  • Inactivation of miR-100 combined with arsenic treatment enhances the malignant transformation of BEAS-2B cells via stimulating epithelial -mesenchymal transition.

    abstract::Chronic arsenic treatment induces epithelial-mesenchymal transition (EMT) and promotes tumorigenicity, but the mechanism is unclear. MiR-100 has been shown to be involved in this biologic process. In this study, we hypothesize that inactivation of miR-100 combined with low concentration of arsenic exposure could promo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Yang J,Chen Z,Wang X,Xu M,Fang H,Li F,Liu Y,Jiang Y,Ding Y,Li J,Wang S

    更新日期:2017-12-02 00:00:00

  • Sorafenib and pemetrexed toxicity in cancer cells is mediated via SRC-ERK signaling.

    abstract::The present studies sought to further understand how the anti-folate pemetrexed and the multi-kinase inhibitor sorafenib interact to kill tumor cells. Sorafenib activated SRC, and via SRC the drug combination activated ERK1/2. Expression of dominant negative SRC or dominant negative MEK1 abolished drug-induced ERK1/2 ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Bareford MD,Hamed HA,Allegood J,Cruickshanks N,Poklepovic A,Park MA,Ogretmen B,Spiegel S,Grant S,Dent P

    更新日期:2012-07-01 00:00:00

  • Cellular adhesion pathways and metastatic potential of human melanoma.

    abstract::Cellular adhesion molecules of the cadherin, integrin, and immunoglobulin superfamilies are important to both growth and metastasis of many cancers, including malignant melanoma. Malignant melanoma is an excellent model for studying these molecules, due in part to a sequential series of five defineable stages. As the ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审


    authors: McGary EC,Lev DC,Bar-Eli M

    更新日期:2002-09-01 00:00:00

  • Systemic and skin toxicity in Cercopithecus aethiops sabaeus monkeys treated during 26 weeks with a high intravenous dose of the anti- epidermal growth factor receptor monoclonal antibody Nimotuzumab.

    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


    authors: Arteaga ME,Ledón N,Casacó A,Pardo B,García M,Boleda M,Viña L,Orphee R,Hernández O,González C,Fuentes D,Rodríguez V,Charro L,Baro F,Macías A,Pérez A,Morales Y,Subirós N,González B,Ramos M,Rodriquez L,Ballester-La

    更新日期:2007-09-01 00:00:00

  • Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes.

    abstract::Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies,...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Nanjappa V,Renuse S,Sathe GJ,Raja R,Syed N,Radhakrishnan A,Subbannayya T,Patil A,Marimuthu A,Sahasrabuddhe NA,Guerrero-Preston R,Somani BL,Nair B,Kundu GC,Prasad TK,Califano JA,Gowda H,Sidransky D,Pandey A,Chatterje

    更新日期:2015-01-01 00:00:00

  • Nucleophosmin/B23, a multifunctional protein that can regulate apoptosis.

    abstract::Nucleophosmin (NPM)/B23, a multifunctional nucleolar protein, is overexpressed in actively proliferating cells and cancer cells. B23 is a tumor marker and exerts its oncogenic effect through binding and suppressing numerous tumor suppressors. NPM-ALK, an aberrant fusion protein produced from t(2;5) translocation in an...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审


    authors: Ye K

    更新日期:2005-09-01 00:00:00

  • The clinical significance of tumor cell-lined vasculature in ovarian carcinoma: implications for anti-vasculogenic therapy.

    abstract::Vasculogenic mimicry reflects the plasticity of aggressive tumor cells that express vascular cell markers and line tumor vasculature; such has been demonstrated in aggressive ovarian carcinoma. This study measured the clinical significance of tumor cell-lined vasculature in ovarian carcinomas (n=77), which was detecte...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Sood AK,Fletcher MS,Zahn CM,Gruman LM,Coffin JE,Seftor EA,Hendrix MJ

    更新日期:2002-11-01 00:00:00

  • Epigenetic changes activate widespread signals in response to double-strand breaks.

    abstract::Double-strand breaks are one the most severe types of DNA damage with respect to cell survival and the preservation of genomic integrity. Therefore, cells have evolved complex mechanisms including cell cycle regulation, activation of repair pathways and in certain cases induction of apoptosis in response to these lesi...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审


    authors: Karagiannis TC,El-Osta A

    更新日期:2004-07-01 00:00:00

  • Tumor suppressor p53 status does not determine the differentiation-associated G₁ cell cycle arrest induced in leukemia cells by 1,25-dihydroxyvitamin D₃ and antioxidants.

    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


    authors: Thompson T,Danilenko M,Vassilev L,Studzinski GP

    更新日期:2010-08-15 00:00:00

  • Drug-induced inactivation or gene silencing of class I histone deacetylases suppresses ovarian cancer cell growth: implications for therapy.

    abstract::There is an urgent need to develop new strategies to treat ovarian cancer, the most deadly gynecologic malignancy. Histone deacetylase (HDAC) inhibitors are emerging as novel therapeutic drugs in the treatment of a variety of cancers, including those resistant to standard chemotherapy. Since there are multiple HDAC is...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Khabele D,Son DS,Parl AK,Goldberg GL,Augenlicht LH,Mariadason JM,Rice VM

    更新日期:2007-05-01 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


    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

  • Targeting adult and pediatric cancers via cell-based vaccines and the prospect of activated B lymphocytes as a novel modality.

    abstract::The delivery of cell-based vaccines that exploit natural mechanisms of antigen presentation represents a promising approach for immunotherapy of cancer. This strategy tests the hypothesis that ex vivo manipulation and reinjection of cellular products can induce immune responses and circumvent immune incompetence to ac...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审


    authors: Coughlin CM,Vonderheide RH

    更新日期:2003-09-01 00:00:00

  • Monoclonal antibodies target intracellular PRL phosphatases to inhibit cancer metastases in mice.

    abstract::PRL-1 (phosphatase of regenerating liver-1), PRL-2 and PRL-3 are protein tyrosine phosphatases with a C-terminal prenylation motif that are localized to the inner leaflet of the plasma membrane and early endosomes. A variety of metastatic PRL-overexpressing cancers have been reported. Therefore, the three PRL-phosphat...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Guo K,Tang JP,Tan CP,Wang H,Zeng Q

    更新日期:2008-05-01 00:00:00

  • CRISPR/Cas9-based Pten knock-out and Sleeping Beauty Transposon-mediated Nras knock-in induces hepatocellular carcinoma and hepatic lipid accumulation in mice.

    abstract::Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Gao M,Liu D

    更新日期:2017-07-03 00:00:00

  • Binding and inhibition of drug transport proteins by heparin: a potential drug transporter modulator capable of reducing multidrug resistance in human cancer cells.

    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


    authors: Chen Y,Scully M,Petralia G,Kakkar A

    更新日期:2014-01-01 00:00:00

  • HIF prolyl hydroxylase-2 inhibition diminishes tumor growth through matrix metalloproteinase-induced TGFβ activation.

    abstract::A right amount of oxygen and nutrients is essential for a tumor to develop. The role of oxygen dependent pathways and their regulators is therefore of utmost importance although little is known about the detailed impact they can have. Recently we have shown that inhibition of the oxygen sensor PHD2 in tumor cells bloc...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Klotzsche-von Ameln A,Muschter A,Heimesaat MM,Breier G,Wielockx B

    更新日期:2012-02-15 00:00:00

  • Production of IL-1β by bone marrow-derived macrophages in response to chemotherapeutic drugs: synergistic effects of doxorubicin and vincristine.

    abstract::Cytotoxic chemotherapeutic drugs, especially when used in combination, are widely employed to treat a variety of cancers in patients but often lead to serious symptoms that negatively affect physical functioning and quality of life. There is compelling evidence that implicates cytotoxic chemotherapy-induced inflammati...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Wong J,Tran LT,Magun EA,Magun BE,Wood LJ

    更新日期:2014-10-01 00:00:00

  • Activation of protein kinase C by phorbol 12-myristate 13-acetate suppresses the growth of lung cancer cells through KLF6 induction.

    abstract::Phorbol 12-myristate 13-acetate (PMA) modulates cell proliferation and survival by activating several intracellular signaling pathways. Protein kinase C (PKC) plays a key role in PMA-induced growth arrest of non-small cell lung cancer (NSCLC) cells. Kruppel-like transcription factor 6 (KLF6), which is associated with ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Tahara E,Kadara H,Lacroix L,Lotan D,Lotan R

    更新日期:2009-05-01 00:00:00

  • FGFR genes mutation is an independent prognostic factor and associated with lymph node metastasis in squamous non-small cell lung cancer.

    abstract::Targeting FGFRs is one of the most promising therapeutic strategies in squamous non-small cell lung cancer (SQCC). However, different FGFR genomic aberrations can be associated with distinct biological characteristics that result in different clinical outcomes or therapeutic consequences. Currently, the full spectrum ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Li JJ,Yan S,Pan Y,Liu Z,Liu Y,Deng Q,Tan Q,Woodward ER,Wu N

    更新日期:2018-01-01 00:00:00

  • mDia function is critical for the cell suicide program triggered by farnesyl transferase inhibition.

    abstract::Farnesyl transferase inhibitors (FTIs) exhibit limited cytotoxic effects against human cancer cells, perhaps explaining the limited efficacy of FTIs in clinical trials. Learning how these well-tolerated drugs trigger p53-independent apoptosis in mouse models of cancer might therefore benefit efforts to leverage their ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Kamasani U,Duhadaway JB,Alberts AS,Prendergast GC

    更新日期:2007-09-01 00:00:00

  • Silencing of heparanase by siRNA inhibits tumor metastasis and angiogenesis of human breast cancer in vitro and in vivo.

    abstract::Expression of the heparanase gene is associated with invasive, angiogenic and metastatic potential of diverse malignant tumors and cell lines. Here we used RNA interference strategies to evaluate the role of human heparanase in breast malignancy and to explore the therapeutic potential of its specific targeting. The s...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Zhang ZH,Chen Y,Zhao HJ,Xie CY,Ding J,Hou YT

    更新日期:2007-04-01 00:00:00

  • Gene expression alterations in formalin-fixed, paraffin-embedded Barrett esophagus and esophageal adenocarcinoma tissues.

    abstract:BACKGROUND AND AIM:Widespread applicability of tissue-based mRNA expression screening for Barrett esophagus (BE) is likely to require (1) accurate methods for assaying archival formalin-fixed, paraffin-embedded (FFPE) histopathology specimens taken at endoscopy, and (2) validation studies of promising biomarkers in dif...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Botelho NK,Schneiders FI,Lord SJ,Freeman AK,Tyagi S,Nancarrow DJ,Hayward NK,Whiteman DC,Lord RV

    更新日期:2010-07-15 00:00:00

  • Tangeretin derivative, 5-acetyloxy-6,7,8,4'-tetramethoxyflavone induces G2/M arrest, apoptosis and autophagy in human non-small cell lung cancer cells in vitro and in vivo.

    abstract::Tangeretin, a major phytochemicals in tangerine peels--an important Chinese herb, has been found to have anti-carcinogenic properties. To improve bioavailability and increase potency of tangeretin, its derivative, 5-acetyloxy-6,7,8,4'-tetramethoxyflavone (5-AcTMF), has been synthesized and shown potent inhibition of p...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Li YR,Li S,Ho CT,Chang YH,Tan KT,Chung TW,Wang BY,Chen YK,Lin CC

    更新日期:2016-01-01 00:00:00

  • Differential impact of fibroblasts on the efficient cell death of lung cancer cells induced by paclitaxel and cisplatin.

    abstract::The efficient treatment of lung carcinomas with chemotherapeutics still poses a challenge for anti-cancer therapy. Since stromal cells of the tumor may alter the responsiveness of tumor cells to chemotherapeutics, we studied the impact of lung fibroblasts (WI-38) on the chemotherapy-induced death of non-small cell lun...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Bartling B,Hofmann HS,Silber RE,Simm A

    更新日期:2008-08-01 00:00:00

  • KLF4 inhibition of lung cancer cell invasion by suppression of SPARC expression.

    abstract::Krüppel-Like Factor 4 (KLF4) functions as a tumor suppressor in some cancers, but its molecular mechanism is not clear. Our recent study also showed that the expression of KLF4 is dramatically reduced in primary lung cancer tissues. To investigate the possible role of KLF4 in lung cancer, we stably transfected KLF4 in...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章


    authors: Zhou Y,Hofstetter WL,He Y,Hu W,Pataer A,Wang L,Wang J,Zhou Y,Yu L,Fang B,Swisher SG

    更新日期:2010-04-01 00:00:00