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dichloroacetate

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https://www.readbyqxmd.com/read/28714513/in-vivo-evaluation-of-tumour-acidosis-for-assessing-the-early-metabolic-response-and-onset-of-resistance-to-dichloroacetate-by-using-magnetic-resonance-ph-imaging
#1
Annasofia Anemone, Lorena Consolino, Laura Conti, Francesca Reineri, Federica Cavallo, Silvio Aime, Dario Livio Longo
Dichloroacetate (DCA) can reverse the glycolytic phenotype that is responsible of increased lactate production and extracellular pH acidification in cancer cells. Magnetic resonance imaging-chemical exchange saturation transfer (MRI-CEST) pH mapping is a novel non-invasive imaging approach that can measure in vivo extracellular tumour pH. We examined whether MRI-CEST pH mapping can monitor in vivo changes in tumour acidosis for assessing treatment response to DCA. Cell viability and extracellular pH were assessed in TS/A breast cancer cells treated with 1-10 mM DCA for 24 h in normoxia or hypoxia (1% O2) conditions...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28672704/control-of-disinfection-byproducts-dbps-by-ozonation-and-peroxone-process-role-of-chloride-on-removal-of-dbp-precursors
#2
Popta Deeudomwongsa, Songkeart Phattarapattamawong, Kun-Yi Andrew Lin
The objective of this study was to remove regulated DBP precursors by using ozonation and peroxone process (H2O2/O3). Regarding formation potentials of trihalomethanes (THMs) and haloacetic acids (HAAs), the role of chloride in chlorination and ozonation/peroxone processes was revealed. The organic compounds in water samples from rapid sand filtration preferably yielded the THM formation potentials, rather than HAAs. Ozonation with the typical applied doses (1-5 mg L(-1)) was ineffective for removals of THM and HAA precursors...
June 26, 2017: Chemosphere
https://www.readbyqxmd.com/read/28654916/inhibition-of-cox2-enhances-the-chemosensitivity-of-dichloroacetate-in-cervical-cancer-cells
#3
Bo Li, Xinzhe Li, Haojun Xiong, Peng Zhou, Zhenhong Ni, Teng Yang, Yan Zhang, Yijun Zeng, Jintao He, Fan Yang, Nan Zhang, Yuting Wang, Yingru Zheng, Fengtian He
Dichloroacetate (DCA), a traditional mitochondria-targeting agent, has shown promising prospect as a sensitizer in fighting against malignancies including cervical cancer. But it is unclear about the effect of DCA alone on cervical tumor. Moreover, previous reports have demonstrated that the increased cyclooxygenase-2 (COX2) expression is associated with chemoresistance and poor prognosis of cervical cancer. However, it is still unknown whether COX2 can affect the sensitivity of DCA in cervical cancer cells...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644886/complex-i-inhibition-augments-dichloroacetate-cytotoxicity-through-enhancing-oxidative-stress-in-vm-m3-glioblastoma-cells
#4
Nathan P Ward, Angela M Poff, Andrew P Koutnik, Dominic P D'Agostino
The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination...
2017: PloS One
https://www.readbyqxmd.com/read/28611197/treatment-of-pancreatic-cancer-patient-derived-xenograft-panel-with-metabolic-inhibitors-reveals-efficacy-of-phenformin
#5
N V Rajeshkumar, Shinichi Yabuuchi, Shweta Pai, Elizabeth De Oliveira, Jurre J Kamphorst, Joshua D Rabinowitz, Héctor Tejero, Fatima Al-Shahrour, Manuel Hidalgo, Anirban Maitra, Chi V Dang
Purpose: To identify effective metabolic inhibitors to suppress the aggressive growth of pancreatic ductal adenocarcinoma (PDAC), we explored the in vivo anti-tumor efficacy of metabolic inhibitors in a panel of patient-derived PDAC xenograft models (PDXs), and investigated whether genomic alterations of tumors correlate with the sensitivity to metabolic inhibitors. <p>Experimental Design: Mice with PDAC tumors from six to thirteen individual PDXs were randomized and treated, once daily for 4 weeks, with either PBS (vehicle) or the glutaminase inhibitor BPTES, transaminase inhibitor aminooxyacetate (AOA), pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA), autophagy inhibitor chloroquine (CQ), mitochondrial complex I inhibitor phenformin/metformin...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28591165/dichloroacetate-affects-proliferation-but-not-apoptosis-in-canine-mammary-cell-lines
#6
Tatjana P Harting, Mandy Stubbendorff, Susanne C Hammer, Patrik Schadzek, Anaclet Ngezahayo, Hugo Murua Escobar, Ingo Nolte
Targeting mitochondrial energy metabolism is a novel approach in cancer research and can be traced back to the description of the Warburg effect. Dichloroacetate, a controversially discussed subject of many studies in cancer research, is a pyruvate dehydrogenase kinase inhibitor. Dichloroacetate causes metabolic changes in cancerous glycolysis towards oxidative phosphorylation via indirect activation of pyruvate dehydrogenase in mitochondria. Canine mammary cancer is frequently diagnosed but after therapy prognosis still remains poor...
2017: PloS One
https://www.readbyqxmd.com/read/28574836/hpv-associated-differential-regulation-of-tumor-metabolism-in-oropharyngeal-head-and-neck-cancer
#7
Young-Suk Jung, Abdo J Najy, Wei Huang, Seema Sethi, Michael Snyder, Wael Sakr, Gregory Dyson, Maik Hüttemann, Icksoo Lee, Rouba Ali-Fehmi, Silvia Franceschi, Linda Struijk, Harold E Kim, Ikuko Kato, Hyeong-Reh Choi Kim
HPV-positive oropharyngeal cancer patients experience significantly lower locoregional recurrence and higher overall survival in comparison with HPV-negative patients, especially among those who received radiation therapy. The goal of the present study is to investigate the molecular mechanisms underlying the differential radiation sensitivity between HPV-negative and HPV-positive head and neck squamous cell carcinoma (HNSCC). Here, we show that HPV-negative HNSCC cells exhibit increased glucose metabolism as evidenced by increased production of lactate, while HPV-positive HNSCC cells effectively utilize mitochondrial respiration as evidenced by increased oxygen consumption...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28572638/mitochondrial-targeting-by-dichloroacetate-improves-outcome-following-hemorrhagic-shock
#8
Kumar Subramani, Sumin Lu, Marie Warren, Xiaogang Chu, Haroldo A Toque, R William Caldwell, Michael P Diamond, Raghavan Raju
Hemorrhagic shock is a leading cause of death in people under the age of 45 and accounts for almost half of trauma-related deaths. In order to develop a treatment strategy based on potentiating mitochondrial function, we investigated the effect of the orphan drug dichloroacetate (DCA) on survival in an animal model of hemorrhagic shock in the absence of fluid resuscitation. Hemorrhagic shock was induced in rats by withdrawing 60% of the blood volume and maintaining a hypotensive state. The studies demonstrated prolonged survival of rats subjected to hemorrhagic injury (HI) when treated with DCA...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28531123/evaluation-of-drinking-water-disinfectant-byproducts-compliance-data-as-an-indirect-measure-for-short-term-exposure-in-humans
#9
Shahid Parvez, Kali Frost, Madhura Sundararajan
In the absence of shorter term disinfectant byproducts (DBPs) data on regulated Trihalomethanes (THMs) and Haloacetic acids (HAAs), epidemiologists and risk assessors have used long-term annual compliance (LRAA) or quarterly (QA) data to evaluate the association between DBP exposure and adverse birth outcomes, which resulted in inconclusive findings. Therefore, we evaluated the reliability of using long-term LRAA and QA data as an indirect measure for short-term exposure. Short-term residential tap water samples were collected in peak DBP months (May-August) in a community water system with five separate treatment stations and were sourced from surface or groundwater...
May 20, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28528979/sensitization-of-breast-cancer-cells-to-paclitaxel-by-dichloroacetate-through-inhibiting-autophagy
#10
Minghao Wang, Cuiwei Liao, Ying Hu, Qinwen Pan, Jun Jiang
Chemotherapy is still the main adjuvant strategy in the treatment of cancer, however, chemoresistance is also frequently encountered. Autophagy inhibition has been widely accepted as a promising therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that dichloroacetate (DCA), a small molecule compound, could significantly inhibit the autophagy induced by Doxorubicin in breast cancer cells. And DCA markedly enhances Doxorubicin-induced breast cancer cell death and anti-proliferation in vitro...
July 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28516168/selective-surface-pegylation-of-uio-66-nanoparticles-for-enhanced-stability-cell-uptake-and-ph-responsive-drug-delivery
#11
Isabel Abánades Lázaro, Salame Haddad, Sabrina Sacca, Claudia Orellana-Tavra, David Fairen-Jimenez, Ross S Forgan
The high storage capacities and excellent biocompatibilities of metal-organic frameworks (MOFs) have made them emerging candidates as drug-delivery vectors. Incorporation of surface functionality is a route to enhanced properties, and here we report on a surface-modification procedure-click modulation-that controls their size and surface chemistry. The zirconium terephthalate MOF UiO-66 is (1) synthesized as ∼200 nm nanoparticles coated with functionalized modulators, (2) loaded with cargo, and (3) covalently surface modified with poly(ethylene glycol) (PEG) chains through mild bioconjugate reactions...
April 13, 2017: Chem
https://www.readbyqxmd.com/read/28505181/overexpression-of-pyruvate-dehydrogenase-kinase-1-in-retinoblastoma-a-potential-therapeutic-opportunity-for-targeting-vitreous-seeds-and-hypoxic-regions
#12
Swatishree Sradhanjali, Devjyoti Tripathy, Suryasnata Rath, Ruchi Mittal, Mamatha M Reddy
Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme implicated in metabolic reprogramming of tumors, is induced in several tumors including glioblastoma, breast cancer and melanoma. However, the role played by PDK1 is not studied in retinoblastoma (RB). In this study, we have evaluated the expression of PDK1 in RB clinical samples, and studied its inhibition as a strategy to decrease cell growth and migration. We show that PDK1 is specifically overexpressed in RB patient samples especially in vitreous seeds and hypoxic regions and cell lines compared to control retina using immunohistochemistry and real-time PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28483502/oxidative-stress-a-key-regulator-of-leiomyoma-cell-survival
#13
Nicole M Fletcher, Mohammed S Abusamaan, Ira Memaj, Mohammed G Saed, Ayman Al-Hendy, Michael P Diamond, Ghassan M Saed
OBJECTIVE: To determine the effects of attenuating oxidative stress with the use of dichloroacetate (DCA) on the expression of key redox enzymes myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) as well as on apoptosis. DESIGN: Prospective experimental study. SETTING: University medical center. PATIENT(S): Cells established from myometrium and uterine fibroid from the same patients. INTERVENTION(S): Cells were exposed to normal (20% O2) or hypoxic (2% O2) conditions for 24 hours with or without DCA (20 μg/mL), a metabolic modulator that shifts anaerobic to aerobic metabolism...
June 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28445868/suppressionof-pyruvate-dehydrogenase-kinase-2-re-sensitizes-paclitaxel-resistant-human-lung-cancer-cells-to-paclitaxel
#14
Hong Sun, Anyou Zhu, Xiang Zhou, Fengchao Wang
Despite impressive initial clinical responses, the majority of lung cancer patients treated with paclitaxel eventually develop resistance to the drug. Pyruvate dehydrogenase kinase-2 (PDK2) is a key regulator of glycolysis and oxidative phosphorylation, and its expression is increased in a variety of tumors. In this study, the role of PDK2 in mediating paclitaxel resistance in lung cancer cells was investigated using biochemical and isotopic tracing methods. Increased expression of PDK2 was observed in paclitaxel-resistant cells ascompared totheir parental cells...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445816/disinfection-byproduct-formation-in-drinking-water-sources-a-case-study-of-yuqiao-reservoir
#15
Hongyan Zhai, Xizhen He, Yan Zhang, Tingting Du, Adeyemi S Adeleye, Yao Li
This study investigated the potential formation of disinfection byproducts (DBPs) during chlorination and chloramination of 20 water samples collected from different points of Yuqiao reservoir in Tianjin, China. The concentrations of dissolved organic matter and ammonia decreased downstream the reservoir, while the specific UV absorbance (SUVA: the ratio of UV254 to dissolved organic carbon) increased [from 0.67 L/(mg*m) upstream to 3.58 L/(mg*m) downstream]. The raw water quality played an important role in the formation of DBPs...
April 15, 2017: Chemosphere
https://www.readbyqxmd.com/read/28431577/dichloroacetic-acid-induced-testicular-toxicity-in-male-rats-and-the-protective-effect-of-date-fruit-extract
#16
Amira El Arem, Lamia Lahouar, Emna Behija Saafi, Amira Thouri, Fatma Ghrairi, Zohra Houas, Fadoua Neffati, Lotfi Achour
BACKGROUND: The present study was designed to investigate the protective effect of aqueous date extract (ADE) against the dichloroacetic acid (DCA)-induced testicular injury in rats. METHODS: Forty-eight male Wistar rats were randomly divided into six groups of eight: group I served as the control; group II was given ADE (4 ml/kg) by gavage; groups III and IV received DCA at 0.5 and 2 g/L drinking water, respectively; and groups V and VI received DCA at 0.5 and 2 g/L drinking water, respectively, before ADE administration...
April 22, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28426747/metabolic-analysis-of-radioresistant-medulloblastoma-stem-like-clones-and-potential-therapeutic-targets
#17
Lue Sun, Takashi Moritake, Kazuya Ito, Yoshitaka Matsumoto, Hironobu Yasui, Hidehiko Nakagawa, Aki Hirayama, Osamu Inanami, Koji Tsuboi
Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76...
2017: PloS One
https://www.readbyqxmd.com/read/28410193/metabolic-targeting-of-egfrviii-pdk1-axis-in-temozolomide-resistant-glioblastoma
#18
Kiran K Velpula, Maheedhara R Guda, Kamlesh Sahu, Jack Tuszynski, Swapna Asuthkar, Sarah E Bach, Justin D Lathia, Andrew J Tsung
Glioblastomas are characterized by amplification of EGFR. Approximately half of tumors with EGFR over-expression also express a constitutively active ligand independent EGFR variant III (EGFRvIII). While current treatments emphasize surgery followed by radiation and chemotherapy with Temozolomide (TMZ), acquired chemoresistance is a universal feature of recurrent GBMs. To mimic the GBM resistant state, we generated an in vitro TMZ resistant model and demonstrated that dichloroacetate (DCA), a metabolic inhibitor of pyruvate dehydrogenase kinase 1 (PDK1), reverses the Warburg effect...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28362300/evaluation-of-dbps-formation-from-smps-exposed-to-chlorine-chloramine-and-ozone
#19
Beibei Zhang, Qiming Xian, Jian Lu, Tingting Gong, Aimin Li, Jianfang Feng
Soluble microbial products (SMPs) are an important group of components in wastewater effluents. In this study, the formation of disinfection by-products (DBPs), including trihalomethanes (THMs), haloacetic acids (HAAs), chlorinated solvents (CSs), haloketones (HKs), haloacetonitriles (HANs) and trichloronitromethane (TCNM) (chloropicrin), from SMPs during chlorination, chloramination and ozonation was investigated. More carbonaceous DBPs (C-DBPs: THMs, HAAs, CSs and HKs) and nitrogenous DBPs (N-DBPs: HANs and TCNM) were formed in chlorination than chloramination...
April 2017: Journal of Water and Health
https://www.readbyqxmd.com/read/28339028/2-methoxyestradiol-enhances-radiosensitivity-in-radioresistant-melanoma-mda-mb-435r-cells-by-regulating-glycolysis-via-hif-1%C3%AE-pdk1-axis
#20
Hong Zhao, Huangang Jiang, Zheng Li, Yafei Zhuang, Yinyin Liu, Shuliang Zhou, Youde Xiao, Conghua Xie, Fuxiang Zhou, Yunfeng Zhou
HIF-1α overexpression is associated with radio-resistance of various cancers. A radioresistant human melanoma cell model MDA-MB-435R (435R) was established by us previously. Compared with the parental cells MDA-MB‑435 (435S), an elevated level of HIF-1α expression in 435R cells was demonstrated in our recent experiments. Therefore, in the current study, we sought to determine whether selective HIF-1α inhibitors could radiosensitize the 435R cells to X-ray, and to identify the potential mechanisms. Our data demonstrated that inhibition of HIF-1α with 2-methoxyestradiol (2-MeOE2) significantly enhanced radiosensitivity of 435R cells...
May 2017: International Journal of Oncology
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