Abstract：
:The multidrug resistance (MDR) phenotype, frequently observed during cancer treatment, is often associated with drug efflux pump activity. However, many other factors are also known to be involved. Cancer cells often rely on aerobic glycolysis for energy production; this is known as the "Warburg effect" and is used as a survival mechanism. Associated to this event, a reverse pH gradient across the cell membrane occurs, leading to cytosol alkalinization and extracellular acidification. In the present study, we investigated the role of different mechanisms involved in MDR, such as altered tumor microenvironment and energetic metabolism. The breast cancer cell line MCF-7, used as model, was exposed to two widely used antitumor drugs, paclitaxel (antimitotic agent) and doxorubicin (alkylating agent). Cancer pH regulation was shown to be crucial for malignant characteristics such as cell migration and drug resistance. Our results showed that a lower extracellular pH induced a higher migratory capacity and higher resistance to the studied chemotherapeutical compounds in MCF-7 cells. Besides the influence of the extracellular pH, the role of the tumor metabolism in the MDR phenotype was also investigated. Pre-treatment with different bioenergetic modulators led to cell ATP depletion and altered lactic acid production and glucose consumption, resulting in increased sensitivity to paclitaxel and doxorubicin. Overall, this study supports the potential use of compounds targeting cell metabolism and tumor microenvironment factors such as pH, as co-adjuvants in conventional chemotherapy.
journal_name
J Bioenerg Biomembrjournal_title
Journal of bioenergetics and biomembranesauthors
Tavares-Valente D,Baltazar F,Moreira R,Queirós Odoi
10.1007/s10863-013-9519-7subject
Has Abstractpub_date
2013-10-01 00:00:00pages
467-75issue
5eissn
0145-479Xissn
1573-6881journal_volume
45pub_type
杂志文章abstract：:2-Arachidonoylglicerol (2-AG) is an endocannabinoid that mimics the pharmacological effects of Δ⁹ tetrahydrocannabinol, the psychoactive component of the plant Cannabis sativa. It is present in many mammalian tissues, such as brain, liver, spleen, heart and kidney, where it exerts different biological effects either r...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/s10863-012-9431-6
更新日期：2012-04-01 00:00:00
abstract：:The purification of the channel-forming component of the mitochondrial calcium uniporter and its channel properties are described. After ethanol and 50% ethanol-water extraction of mitochondria from beef heart or perfused rat liver, the extract was passed through thiopropyl-Sepharose 6B column, and absorbed components...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/BF00763072
更新日期：1994-04-01 00:00:00
abstract：:Evidence suggests membrane bound F(1)F(0)-ATPase complexes form stable associations such that dimers can be retrieved from detergent lysates of mitochondria isolated from a range of sources including algae, higher plants, yeast and bovine heart, and plant chloroplasts. The physiological relevance of these interactions...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/s10863-005-4128-8
更新日期：2005-04-01 00:00:00
abstract：:Bacillus subtilis has a bifurcated respiratory chain composed of a cytochrome branch and a quinol oxidase branch. The respiratory complexes of this bacterium have been elucidated mostly by the analysis of the genome and by the isolation of individual complexes. The supramolecular organization of this respiratory chain...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/s10863-012-9454-z
更新日期：2012-08-01 00:00:00
abstract：:Cyclosporin A (CsA) is highly neuroprotective in several animal models of acute neurological damage and neurodegenerative disease with inhibition of the mitochondrial permeability transition (mPT) having emerged as a possible mechanism for the observed neuroprotection. In the present study, we have evaluated two new n...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1023/B:JOBB.0000041776.31885.45
更新日期：2004-08-01 00:00:00
abstract：:The P515 absorbance change upon single-turnover light flashes has been studied in intact leaves and isolated chloroplasts from spinach. A comparative study of the effects of preillumination on the kinetics of the P515 response and on the activity of the chloroplast ATPase has been made. The slow component (reaction 2)...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/BF00751054
更新日期：1983-12-01 00:00:00
abstract：:NM23s (or NDP kinases) regulate a fascinating variety of cellular activities, including proliferation, development, and differentiation. All these processes are modulated by external stimuli, leading to the idea that this family of proteins modulates transmembrane signaling pathways. This review summarizes the evidenc...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1023/a:1005589029959
更新日期：2000-06-01 00:00:00
abstract：:Hepatic iron toxicity because of iron overload seems to be mediated by lipid peroxidation of biological membranes and the associated organelle dysfunctions. However, the basic mechanisms underlying this process in vivo are still little understood. Gerbils were dosed with weekly injections of iron-dextran alone or in c...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1023/a:1005512014280
更新日期：2000-04-01 00:00:00
abstract：:Two kinds of ATP binding sites were found on the ATPase molecule in deoxycholic acid-treated sarcoplasmic reticulum. One was the catalytic site (1 mol/mol active site) and its affinity was high. Upon addition of Ca2+, all the ATP bound to the catalytic site disappeared at 75 mM KCl, while a significant amount of ATP r...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/BF00743060
更新日期：1982-12-01 00:00:00
abstract：:Arsenic trioxide is an effective treatment for acute promyelocytic leukemia, but resistance to metalloid salts is found in humans. Using atomic absorption spectroscopy, we have measured the rate of uptake of arsenic trioxide and of antimony tartrate in GLC4 and GLC4/ADR cells overexpressing MRP1 and the rate of their ...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1023/a:1015180026665
更新日期：2002-04-01 00:00:00
abstract：:First, halorhodopsin is capable of pumping protons after illumination with green and blue light in the same direction as chloride. Second, mutated bacteriorhodopsin where the proton acceptor Asp85 and the proton donor Asp96 are replaced by Asn showed proton pump activity after illumination with blue light in the same ...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/BF00762676
更新日期：1992-04-01 00:00:00
abstract：:The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis. UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes. O-GlcNAc transferase (OGT...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/s10863-018-9747-y
更新日期：2018-06-01 00:00:00
abstract：:3-Bromopyruvate (3BP) is an energy-depleting drug that inhibits Hexokinase II activity by alkylation during glycolysis, thereby suppressing the production of ATP and inducing cell death. As such, 3BP can potentially serve as an anti-tumorigenic agent. Our previous research showed that 3BP can induce apoptosis via AKT ...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/s10863-015-9612-1
更新日期：2015-08-01 00:00:00
abstract：:Beef heart cytochrome c oxidase was reconstituted in asolectin liposomes containing the pH indicator fluorescein-phosphatidylethanolamine (FPE) by the cholate-dialysis procedure. The influence of FPE on the asolectin liposome size and of the removal of subunit III from the complex on its incorporation into liposomes w...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/BF00743111
更新日期：1985-12-01 00:00:00
abstract：:The topology of beef heart Complex III has been studied by tryptic and chymotryptic digestion of isolated Complex III, Mg2+-ATP submitochondrial particles, and mitoplasts. Degradation products were detected by the immunoreplication technique using specific antibodies against core protein 1 (50 K) and core protein 2 (4...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/BF00743485
更新日期：1983-02-01 00:00:00
abstract：:Proton transport-coupled unisite catalysis was measured with the H(+)-ATPase from chloroplasts. The reaction was measured in the ATP hydrolysis direction under deenergized conditions and in the ATP synthesis direction under energized conditions. The equilibrium constant of the enzyme does not change upon energization,...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/BF00762367
更新日期：1992-10-01 00:00:00
abstract：:Cellular Ca2+ signals are crucial in the control of most physiological processes, cell injury and programmed cell death; mitochondria play a pivotal role in the regulation of such cytosolic Ca2+ ([Ca2+]c) signals. Mitochondria are endowed with multiple Ca2+ transport mechanisms by which they take up and release Ca2+ a...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1023/a:1005508311495
更新日期：2000-02-01 00:00:00
abstract：:We have studied changes in plasma membrane NAD(P)H:quinone oxidoreductases of HL-60 cells under serum withdrawal conditions, as a model to analyze cell responses to oxidative stress. Highly enriched plasma membrane fractions were obtained from cell homogenates. A major part of NADH-quinone oxidoreductase in the plasma...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1023/a:1016035504049
更新日期：2002-06-01 00:00:00
abstract：:The inner membrane of yeast and mammalian mitochondria has been studied in situ with a patch clamp electrode. Anion channels were found in both cases, although their behavior and regulation are different. In mammalian mitochondria, the principal channel is of around 100 pS conductance and opens mainly under depolarize...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/BF02110642
更新日期：1996-04-01 00:00:00
abstract：:Traditionally, mitochondria have been viewed as the "powerhouse" of the cell, i.e., the site of the oxidative phosphorylation machinery involved in ATP production. Consequently, much of the research conducted on mitochondria over the past 4 decades has focused on elucidating both those molecular events involved in ATP...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1023/a:1005453700533
更新日期：1999-08-01 00:00:00
abstract：:Electron microscopy (EM) in combination with image analysis is a powerful technique to study protein structure at low- and high resolution. Since electron micrographs of biological objects are very noisy, substantial improvement of image quality can be obtained by averaging individual projections. Crystallographic and...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/BF00763217
更新日期：1994-02-01 00:00:00
abstract：:Mitochondria, isolated from the ubiquinone-deficient nuclear mutant of Saccharomyces cerevisiae E3-24, are practically unable to oxidize exogenous substrates. Respiratory activity, coupled to ATP synthesis, can, however, be reconstituted by the simple addition of ethanolic solutions of ubiquinones. A minimal length of...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/BF00745017
更新日期：1982-06-01 00:00:00
abstract：:Vacuolar H+ ATPases participate in renal hydrogen ion secretion in both the proximal and distal nephron. These plasma membrane forms of the vacuolar H+ ATPase are regulated physiologically to maintain the acid-base balance of the organism. Proton transporting renal cells have requirements for constitutive acidificatio...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/BF00762528
更新日期：1992-08-01 00:00:00
abstract：:Recent studies of isolated muscle membrane have enabled induction and monitoring of rapid Ca2+ release from sarcoplasmic reticulum (SR)5 in vitro by a variety of methods. On the other hand, various proteins that may be directly or indirectly involved in the Ca2+ release mechanism have begun to be unveiled. In this min...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/BF00812071
更新日期：1989-04-01 00:00:00
abstract：:The term "direct-coupled" is considered in the context of redox-linked proton translocation mechanisms, and the origins of this concept, its philosophical implications, applications, and contributions to the development of bioenergetics, are discussed. ...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/BF00785997
更新日期：1991-10-01 00:00:00
abstract：:Mitochondrial impairment has been collecting more and more attention as a contributing factor to the etiology of Parkinson's disease. Above all, the NADH-quinone oxidoreductase, complex I, of the respiratory chain seems to be most culpable. Complex I dysfunction is translated to an increased production of reactive oxy...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/s10863-009-9249-z
更新日期：2009-12-01 00:00:00
abstract：:A study of NADH ferricyanide reductase activity in oriented vesicles or open ghosts of human and porcine erythrocytes shows that the dehydrogenase activity can have three types of orientation in the membrane. There is activity which responds only to acceptors and NADH exclusively on the inside face, or exclusively on ...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/BF00743068
更新日期：1982-12-01 00:00:00
abstract：:The presence of transplasma membrane electron transport in a variety of plant cells and tissues is reported. It is now agreed that this property of eukaryotic cells is of ubiquitous nature. Studies with highly purified plasma membranes have established the presence of electron transport enzymes. Two types of activitie...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/BF00771013
更新日期：1991-06-01 00:00:00
abstract：:The ATP synthetase of chloroplast membranes binds ADP and ATP with high affinity, and the binding becomes quasi-irreversible under certain conditions. One explanation of the function of these nucleotides is that they are transiently tightly bound during ATP synthesis as part of the catalytic process, and that the rele...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章
doi：10.1007/BF00744524
更新日期：1983-10-01 00:00:00
abstract：:The production of all blood cells from hematopoietic stem cells (HSC) is highly sensitive to reactive oxygen species (ROS). Cumulating evidence suggests that mitochondria are critical for HSC fate determination. FOXO are known regulators of anti-oxidant response and key to the maintenance of HSC. Recent works indicate...
journal_title：Journal of bioenergetics and biomembranes
pub_type： 杂志文章,评审
doi：10.1007/s10863-017-9719-7
更新日期：2017-08-01 00:00:00
