• Title/Summary/Keyword: Warburg effect

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Cancer Metabolism: Strategic Diversion from Targeting Cancer Drivers to Targeting Cancer Suppliers

  • Kim, Soo-Youl
    • Biomolecules & Therapeutics
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    • 제23권2호
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    • pp.99-109
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    • 2015
  • Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.

Cancer Metabolism: Fueling More than Just Growth

  • Lee, Namgyu;Kim, Dohoon
    • Molecules and Cells
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    • 제39권12호
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    • pp.847-854
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    • 2016
  • The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slowergrowing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates that altered metabolism plays key roles in supporting proliferation-independent functions of cancer such as cell survival within the ischemic and acidic tumor microenvironment, immune system evasion, and maintenance of the cancer stem cell state. As these aspects of cancer cell metabolism are critical for tumor maintenance yet are less likely to be relevant in normal cells, they represent attractive targets for cancer therapy.

Chlorella의 생리에 미치는 Indole acetic acid의 영향 (Physiological effects of indole acetic acid (IAA) on chlorella ellipsoidea)

  • 채인기
    • 미생물학회지
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    • 제10권3호
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    • pp.117-127
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    • 1972
  • To study the effect of IAA on the growth of Chlorella, the alage wre cultured on the media for six days by bubbling $_{2}$ enriched air under 10K lux at 20-$25^{\circ}C$. The culture media were made by adding a concentration of $10^{-3}$M, $10^{-4}$M, and 0M(as a control) IAA to the standard media. During the period of culture, Chlorella was smapled for the given time of interval and photosynthetic and respiratory activities were measured by Warburg manometer and change of chemical components of Chlorella was determined by spectrophotometry after the Chlorella cell was fractionated by Schmidt-Thannhauser method. 1) Photosynthetic and respiratory activities were enhanced by IAA ; especially the enhancement of respiratory activity was so remarkable. 2) As to the chemical components of Chlorella, carbohydrates and amino acids were reduced a little but phosphate, RNA, DNA, and protein were increased by $10^{-3}$M IAA ; the increase of RNA, in particular, was noticable. 3) The above results suggest that the enhancement of growth of Chlorella, by IAA and ATP induced by respiratory activity accelerated with IAA enhanced RNA synthesis, resulting in an increase of protein synthesis.

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탄수화물과 황산암모늄이 Pseudomonas diminuta의 리그닌 분해에 미치는 영향 (Effects of Some Carbohydrates and Ammonium Sulfate on Lignin Degradation by Pseudomonas diminuta)

  • 김규중;신광수;맹진수;성치남
    • 미생물학회지
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    • 제26권2호
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    • pp.129-136
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    • 1988
  • To investigate the influence of cosubstrate supplement and ammonium sulfate on lignin degradation by Pseudomonas diminuta KM-4-2, isolated in the laboratory, the strain was cultured on the lignin media which contained lignin as a source of carbon and the culture filtrate was analyzed by Sephadex G-75 column chromatography. It was found that polymerization was not appeared unlike wood-rot fungi. When the carbohydrates were added, the peak of lignin at 280nm by UV scanning spectra of the filtrate, was significantly increased. In order to determine the effect of ammonium sulfate on the ligninolytic activity, the isolated strain was incubated in the media containing 0.1%, 0.25% and 0.5% of nitrogen concentration in the Warburg flask and the rate of oxygen uptake was esitmated by Warbuge Respirometer. As a result, the activity was maximum at 0.1% of nitrogen concentration and thereafter decreased in parallel with nitrogen concentration.

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Tumor bioenergetics: An emerging avenue for cancer metabolism targeted therapy

  • Kee, Hyun Jung;Cheong, Jae-Ho
    • BMB Reports
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    • 제47권3호
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    • pp.158-166
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    • 2014
  • Cell proliferation is a delicately regulated process that couples growth signals and metabolic demands to produce daughter cells. Interestingly, the proliferation of tumor cells immensely depends on glycolysis, the Warburg effect, to ensure a sufficient amount of metabolic flux and bioenergetics for macromolecule synthesis and cell division. This unique metabolic derangement would provide an opportunity for developing cancer therapeutic strategy, particularly when other diverse anti-cancer treatments have been proved ineffective in achieving durable response, largely due to the emergence of resistance. Recent advances in deeper understanding of cancer metabolism usher in new horizons of the next generation strategy for cancer therapy. Here, we discuss the focused review of cancer energy metabolism, and the therapeutic exploitation of glycolysis and OXPHOS as a novel anti-cancer strategy, with particular emphasis on the promise of this approach, among other cancer metabolism targeted therapies that reveal unexpected complexity and context-dependent metabolic adaptability, complicating the development of effective strategies.

Lactate: a multifunctional signaling molecule

  • Lee, Tae-Yoon
    • Journal of Yeungnam Medical Science
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    • 제38권3호
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    • pp.183-193
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    • 2021
  • Since its discovery in 1780, lactate has long been misunderstood as a waste by-product of anaerobic glycolysis with multiple deleterious effects. Owing to the lactate shuttle concept introduced in the early 1980s, a paradigm shift began to occur. Increasing evidence indicates that lactate is a coordinator of whole-body metabolism. Lactate is not only a readily accessible fuel that is shuttled throughout the body but also a metabolic buffer that bridges glycolysis and oxidative phosphorylation between cells and intracellular compartments. Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells and tissues, resulting in diverse biological consequences including decreased lipolysis, immune regulation, anti-inflammation, wound healing, and enhanced exercise performance in association with the gut microbiome. Furthermore, lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones, accounting for its key role in immune modulation and maintenance of homeostasis.

Pseudomonas fluorescens에 대한 furfural의 독성효과에 관하여 (Toxic effects of furfural on Pseudomonas fluorescens)

  • 김태용;하영칠;홍순우
    • 미생물학회지
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    • 제21권3호
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    • pp.149-155
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    • 1983
  • Furfural을 유일한 탄소원으로 이용하지 뭇하는 것으로 알려졌던 Pseudomonas jlµorescens가 호조건하에서 저농도의 furfural은 이용가능함을 밝혔다. 이 균주가 고농도의 furfural은 잘 이용하지 못하는 것은 furfural이 균주에 대해 다음과 같은 독성효과를 나타내기 때문이다. 1. 0.01% 정도의 furfural에 의해서 잠재기가 연장되었고 특히 생장초기의 균체에 더 큰 억제효과가 나타나 잠재기의 연장과 동시에 균체수율도 감소하였다. 2. 0.1% 이상의 furfural은 치사효과를 나타냈으며 대사활성도가 클수록 치사율이 높았고 치사율에 차이가 나타나 생장초기의 균체가 더 큰 치사율을 나타냈다. 3. Furfural이 호흡률에 대해서는 별다른 영향을 나타내지 않았다.

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적층가공된 티타늄 합금의 전기화학적 특성에 미치는 불산의 영향 (Effect of Hydrofluoric Acid on the Electrochemical Properties of Additive Manufactured Ti and Its Alloy)

  • 김기태;조현우;장현영;김영식
    • Corrosion Science and Technology
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    • 제17권4호
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    • pp.166-175
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    • 2018
  • In this study, the electrochemical properties of CP-Ti (commercially pure titanium) and Ti-64 (Ti-6Al-4V) were evaluated and the effect of hydrofluoric acid on corrosion resistance and electrochemical properties was elucidated. Additive manufactured materials were made by DMT (Directed Metal Tooling) method. Samples were heat-treated for 1 hour at $760^{\circ}C$ and then air cooled. Surface morphologies were studied by optical microscope and SEM. Electrochemical properties were evaluated by anodic polarization method and AC-impedance measurement. The oxide film formed on the surface was analyzed using an XPS. The addition of HF led to an increase in the passive current density and critical current density and decreased the polarization resistance regardless of the alloys employed. Based on the composition of the oxide film, the compositional difference observed by the addition of HF was little, regardless of the nature of alloys. The Warburg impedance obtained by AC-impedance measurement indicates the dissolution of the constituents of CP-Ti and Ti-64 through a porous oxide film.

Convergence of Cancer Metabolism and Immunity: an Overview

  • Van Dang, Chi;Kim, Jung-whan
    • Biomolecules & Therapeutics
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    • 제26권1호
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    • pp.4-9
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    • 2018
  • Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

Application of Generalized Transmission Line Models to Mixed Ionic-Electronic Transport Phenomena

  • Ahn, Pyung-An;Shin, Eui-Chol;Kim, Gye-Rok;Lee, Jong-Sook
    • 한국세라믹학회지
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    • 제48권6호
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    • pp.549-558
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    • 2011
  • Application of a generalized equivalent circuit including the electrode condition for the Hebb-Wagner polarization in the frequency domain proposed by Jamnik and Maier can provide a consistent set of material parameters, such as the geometric capacitance, partial conductivities, chemical capacitance or diffusivity, as well as electrode characteristics. Generalization of the shunt capacitors for the chemical capacitance by the constant phase elements (CPEs) was applied to a model mixed conducting system, $Ag_2S$, with electron-blocking AgI electrodes and ion-blocking Pt electrodes. While little difference resulted for the electron-blocking cell with almost ideal Warburg behavior, severely non-ideal behavior in the case of Pt electrodes not only necessitates a generalized transmission line model with shunt CPEs but also requires modelling of the leakage in the cell approximately proportional to the cell conductance, which then leads to partial conductivity values consistent with the electron-blocking case. Chemical capacitance was found to be closer to the true material property in the electron-blocking cell while excessively high chemical capacitance without expected silver activity dependence resulted in the electron-blocking cell. A chemical storage effect at internal boundaries is suggested to explain the anomalies in the respective blocking configurations.