Abstract:
:Although the "Warburg effect", i.e., elevated glucose metabolism to lactic acid (glycolysis) even in the presence of oxygen, has been recognized as the most common biochemical phenotype of cancer for over 80 years, its biochemical and genetic basis remained unknown for over 50 years. Work focused on elucidating the underlying mechanism(s) of the "Warburg effect" commenced in the author's laboratory in 1969. By 1985 among the novel findings made two related most directly to the basis of the "Warburg effect", the first that the mitochondrial content of tumors exhibiting this phenotype is markedly decreased relative to the tissue of origin, and the second that such mitochondria have markedly elevated amounts of the enzyme hexokinase-2 (HK2) bound to their outer membrane. HK2 is the first of a number of enzymes in cancer cells involved in metabolizing the sugar glucose to lactic acid. At its mitochondrial location HK2 binds at/near the protein VDAC (voltage dependent anion channel), escapes inhibition by its product glucose-6-phosphate, and gains access to mitochondrial produced ATP. As shown by others, it also helps immortalize cancer cells, i.e., prevents cell death. Based on these studies, the author's laboratory commenced experiments to elucidate the gene basis for the overexpression of HK2 in cancer. These studies led to both the discovery of a unique HK2 promoter region markedly activated by both hypoxic conditions and moderately activated by several metabolites (e.g., glucose), Also discovered was the promoter's regulation by epigenetic events (i.e., methylation, demethylation). Finally, the author's laboratory turned to the most important objective. Could they selectively and completely destroy cancerous tumors in animals? This led to the discovery in an experiment conceived, designed, and conducted by Young Ko that the small molecule 3-bromopyruvate (3BP), the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent. Significantly, in subsequent experiments with rodents (19 animals with advanced cancer) Ko led a project in which 3BP was shown in a short treatment period to eradicate all (100%). Ko's and co-author's findings once published attracted global attention leading world-wide to many other studies and publications related to 3BP and its potent anti-cancer effect. This Issue of the Journal of Bioenergetics and Biomembranes (JOBB 44-1) captures only a sampling of research conducted to date on 3BP as an anticancer agent, and includes also a Case Report on the first human patient known to the author to be treated with specially formulated 3BP. Suffice it to say in this bottom line, "3BP, a small molecule, results in a remarkable therapeutic effect when it comes to treating cancers exhibiting a "Warburg effect". This includes most cancer types.
journal_name
J Bioenerg Biomembrjournal_title
Journal of bioenergetics and biomembranesauthors
Pedersen PLdoi
10.1007/s10863-012-9425-4subject
Has Abstractpub_date
2012-02-01 00:00:00pages
1-6issue
1eissn
0145-479Xissn
1573-6881journal_volume
44pub_type
社论abstract::Members of the genus Methanosarcina are strictly anaerobic archaea that derive their metabolic energy from the conversion of a restricted number of substrates to methane. H2 + CO2 are converted to CH4 via the CO2-reducing pathway, while methanol and methylamines are metabolized by the methylotrophic pathway. Two novel...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1023/b:jobb.0000019598.64642.97
更新日期:2004-02-01 00:00:00
abstract::The human multidrug resistance protein, or P-glycoprotein (Pgp), exhibits a high-capacity drug-dependent ATP hydrolytic activity that is a direct reflection of its drug transport capability. This activity is readily measured in membranes isolated from cultured insect cells infected with a baculovirus carrying the huma...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/BF02110329
更新日期:1995-02-01 00:00:00
abstract::The molecular mechanism by which the membrane-embedded FO sector of the mitochondrial ATP synthase translocates protons, thus dissipating the transmembrane protonmotive force and leading to ATP synthesis, involves the neutralization of the carboxylate residues of the c-ring. Carboxylates are thought to constitute the ...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/s10863-013-9504-1
更新日期:2013-06-01 00:00:00
abstract::The mitochondrial UPR (UPRmt) is rapidly gaining attention. While most studies on the UPRmt have focused on its role in aging, emerging studies suggest an important role of the UPRmt in cancer. Further, several of the players of the UPRmt in mammalian cells have well reported roles in the maintenance of the organelle....
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/s10863-017-9722-z
更新日期:2017-08-01 00:00:00
abstract::Transformation of 3T3 cells by SV40 virus changes the properties of the transplasma membrane electron transport activity which can be assayed by reduction of external ferric salts. After 42 h of culture and before the growth rate is maximum, the transformed cells have a much slower rate of ferric reduction. The change...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/BF00786008
更新日期:1991-12-01 00:00:00
abstract::In order to determine whether polymorphic forms of the Ca2+ + Mg2+-dependent ATPase exist, we have examined the cross-reactivity of five monoclonal antibodies prepared against the rabbit skeletal muscle sarcoplasmic reticulum enzyme with proteins from microsomal fractions isolated from a variety of muscle and nonmuscl...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/BF00743238
更新日期:1984-12-01 00:00:00
abstract::By manipulating the physical properties of oxygen, cells are able to harvest the large thermodynamic potential of oxidation to provide a substantial fraction of the energy necessary for cellular processes. The enzyme largely responsible for this oxygen manipulation is cytochrome c oxidase, which resides at the inner m...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/s10863-007-9084-z
更新日期:2007-06-01 00:00:00
abstract::The transport systems of animal and human tissues for vitamin C are reviewed with respect to their properties. It emerges that pure diffusion plays only a very minor role while a variety of more or less specific transporters is found on cellular membranes. Although most tissues prefer the reduced ascorbate over the ox...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/BF00762776
更新日期:1994-08-01 00:00:00
abstract::The cytochrome b6/f complex of higher plant chloroplasts is uniformly distributed throughout both appressed and nonappressed thylakoids, in contrast to photosystem II and photosystem I, the other major membrane protein complexes involved in electron transport. We discuss how this distribution is likely to affect inter...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/BF00743013
更新日期:1986-10-01 00:00:00
abstract::Due to the high metabolic demands of the placental tissue during gestation, we decide to analyzed the mitochondrial bioenergetic functions in the human term placenta. Different mitochondrial morphological parameters, membrane potential and cardiolipin content were determined by flow cytometry. Oxygen uptake, hydrogen ...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/s10863-014-9572-x
更新日期:2014-12-01 00:00:00
abstract::Complex I (NDH-1) translocates protons across the membrane using electron transfer energy. Two different coupling mechanisms are currently being discussed for complex I: direct (redox-driven) and indirect (conformation-driven). Semiquinone (SQ) intermediates are suggested to be key for the coupling mechanism. Recently...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/s10863-014-9557-9
更新日期:2014-08-01 00:00:00
abstract::Plasma membranes isolated from pig liver contained almost no acid sphingomyelinase but significant neutral magnesium-dependent sphingomyelinase that was activated by phosphatidylserine. We report here the purification to apparent homogeneity of neutral sphingomyelinase of about 87 kDa from liver plasma membranes. The ...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1023/a:1010704715979
更新日期:2001-04-01 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::The fungal plasma membrane contains a proton-translocating ATPase that is closely related, both structurally and functionally, to the [Na+, K+]-, [H+, K+]-, and [Ca2+]-ATPases of animal cells, the plasma-membrane [H+]-ATPase of higher plants, and several bacterial cation-transporting ATPases. This review summarizes cu...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/BF00808117
更新日期:1989-10-01 00:00:00
abstract::Cytochrome c oxidase was purified from mitochondria of Euglena gracilis and separated into 15 different polypeptide subunits by polyacrylamide gel electrophoresis. All 15 subunits copurify through various purification procedures, and the subunit composition of the isolated enzyme is identical to that of the immunoprec...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/BF00762727
更新日期:1989-06-01 00:00:00
abstract::This study was designed to investigate the energetics of isolated rat hepatocyte swelling due to sodium-cotransported amino acid accumulation in a medium containing either glucose or octanoate as basal substrate. We show that the size of the increase in cytosolic volume is directly correlated with the total amino acid...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1023/a:1022487119390
更新日期:1997-12-01 00:00:00
abstract::Advanced glycation end products (AGEs) and methylglyoxal (MG), an important intermediate in AGEs synthesis, are thought to contribute to protein aging and to the pathogenesis of age-and diabetes-associated complications. This study was intended to investigate brain mitochondria bioenergetics and oxidative status of ra...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/s10863-014-9551-2
更新日期:2014-10-01 00:00:00
abstract::As the terminal component of the mitochondrial respiratory chain, cytochrome c oxidase plays a vital role in cellular energy transformation. Human cytochrome c oxidase is composed of 13 subunits. The three major subunits form the catalytic core and are encoded by mitochondrial DNA (mtDNA). The remaining subunits are n...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1023/a:1022638013825
更新日期:1997-04-01 00:00:00
abstract::Phosphatase activity of a kidney (Na + K)-ATPase preparation was optimally active with Mg2+ plus K+. Mn2+ was less effective and Ca2+ could not substitute for Mg2+. However, adding Ca2+ with Mg2+ or substituting Mn2+ for Mg2+ activated it appreciably in the absence of added K+, and all three divalent cations decreased...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/BF00751061
更新日期:1985-06-01 00:00:00
abstract::The mitochondrial inner membrane anion channel (IMAC) is a channel, identified by flux studies in intact mitochondria, which has a broad anion selectivity and is maintained closed or inactive by matrix Mg2+ and H+. We now present evidence that this channel, like many other chloride/anion channels, is reversibly blocke...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/BF02110652
更新日期:1996-04-01 00:00:00
abstract::The purpose of this study was to characterize the physical properties of cytochrome c oxidase from rat liver. The enzyme was extracted from isolated mitochondria with nonionic detergents and further purified by ion-exchange chromatography on DEAE Bio-Gel A. The purified enzyme contained 9.64 nmol heme a/mg protein and...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/BF00743154
更新日期:1977-08-01 00:00:00
abstract::A series of amphiphilic polymethlyenecarboxymaleimides has been synthesized for use as sulfhydryl reagents applicable to membrane proteins. Physical properties of the compounds which are relevant to their proposed mode of action have been determined. By comparing rates of reaction in aqueous and aprotic solvents, the ...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/BF00809072
更新日期:1990-10-01 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
abstract::Overexpression of the Homo sapiens LYR motif containing 1 (LYRM1) causes mitochondrial dysfunction and induces insulin resistance in 3T3-L1 adipocytes. α-Lipoic acid (α-LA), a dithiol compound with antioxidant properties, improves glucose transport and utilization in 3T3-L1 adipocytes. The aim of this study was to inv...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/s10863-012-9460-1
更新日期:2012-10-01 00:00:00
abstract::Epilepsy is a neurological disorder characterized by spontaneous, recurrent and paroxysmal cerebral discharge, clinically leading to persistent alterations in function and morphology of neurons. Oxidative stress is one of possible mechanisms in the pathogenesis of epilepsy. Oxidative stress resulting from mitochondria...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/s10863-010-9317-4
更新日期:2010-12-01 00:00:00
abstract::Many previous investigations have consistently reported that caloric restriction (40%), which increases maximum longevity, decreases mitochondrial reactive species (ROS) generation and oxidative damage to mitochondrial DNA (mtDNA) in laboratory rodents. These decreases take place in rat liver after only seven weeks of...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/s10863-006-9051-0
更新日期:2006-12-01 00:00:00
abstract::Reconstitution experiments were performed on lipid bilayer membranes in the presence of purified mitochondrial porin from yeast and of detergent-solubilized mitochondrial outer membranes of a porin-free yeast mutant. The addition of the porin resulted in a strong increase of the membrane conductance, which was caused ...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/BF00762516
更新日期:1989-08-01 00:00:00
abstract::Liver plasma membranes isolated from rats with chronic dietary iron overload showed a large modification of their phospholipid fatty acid composition. Specifically, a significant decrease in polyunsaturated fatty acids and a parallel increase in saturated fatty acids was observed. This pattern was consistent with the ...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章
doi:10.1007/BF00762524
更新日期:1989-08-01 00:00:00
abstract::Many oxidoreductases are constructed from (a) local sites of strongly coupled substrate-redox cofactor partners participating in exchange of electron pairs, (b) electron pair/single electron transducing redox centers, and (c) nonadiabatic, long-distance, single-electron tunneling between weakly coupled redox centers. ...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/BF02110096
更新日期:1995-06-01 00:00:00
abstract::There has been increased interest in the use of naturally occurring compounds with chemopreventive and chemotherapeutic effects in the treatment of cancers. This review summarizes the most recent advances that provide new insights into the molecular mechanisms underlying the apoptotic potential of nutritional suppleme...
journal_title:Journal of bioenergetics and biomembranes
pub_type: 杂志文章,评审
doi:10.1007/s10863-006-9056-8
更新日期:2007-02-01 00:00:00