• Proceedings of the PSK Conference
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• 2000.10a
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• pp.269.1-269.1
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• 2000

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.1
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• pp.15-24
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• 2022

The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-H₃R₉ exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy. In viability assays, GA-MTS-H₃R₉ showed a better rescue action compared to that of MTS-H₃R₉. GA-MTS-H₃R₉ dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-H₃R₉ towards mitochondria in AC16 cells. Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTS-H₃R₉ alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-H₃R₉ showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-H₃R₉. We showed that GA-MTS-H₃R₉ can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.3 no.1
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• pp.58-61
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• 2003

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.10-18
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• 2018

Tumors are dynamic metabolic systems which highly augmented metabolic fluxes and nutrient needs to support cellular proliferation and physiological function. For many years, a central hallmark of tumor metabolism has emphasized a uniformly elevated aerobic glycolysis as a critical feature of tumorigenecity. This led to extensive efforts of targeting glycolysis in human cancers. However, clinical attempts to target glycolysis and glucose metabolism have proven to be challenging. Recent advancements revealing a high degree of metabolic heterogeneity and plasticity embedded among various human cancers may paint a new picture of metabolic targeting for cancer therapies with a renewed interest in glucose metabolism. In this review, we will discuss diverse oncogenic and molecular alterations that drive distinct and heterogeneous glucose metabolism in cancers. We will also discuss a new perspective on how aberrantly altered glycolysis in response to oncogenic signaling is further influenced and remodeled by dynamic metabolic interaction with surrounding tumor-associated stromal cells.

• Journal of Korean Traditional Oncology
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• v.20 no.1
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• pp.81-88
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• 2015

Generally, normal cells synthesize adenosine triphosphate (ATP) through oxidative phosphorylation in the mitochondria. However, they produce ATP through lactic acid fermentation on hypoxic condition. Interestingly, many cancer cells rely on aerobic glycolysis for ATP generation instead of mitochondrial oxidative phosphorylation, which is termed as "Warburg effect". According to results from recent researches on differences of cancer cell metabolism from normal cell metabolism and because chemotherapy to suppress rapidly growing cells, as a side effect of cancer treatment, can still target healthy cells, there is merit in the development of small-molecule inhibitors targeting metabolic enzymes such as pyruvate dehydrogenase kinase (PDHK), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT). For new anticancer therapy, in this review, we show recent advances in study on cancer cell metabolism and molecules targeting metabolic enzymes which are importantly associated with cancer metabolism for cancer therapy. Furthermore, we would also like to emphasize the necessity of development of molecules targeting metabolic enzymes using herbal medicines and their constituents for anticancer drugs.

• Biomolecules & Therapeutics
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• v.23 no.2
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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.

• Biomedical Science Letters
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• v.23 no.3
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• pp.166-174
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• 2017

The bacterial cells located within the gastrointestinal tract (GIT) outnumber the host's cells by a factor of ten. These human digestive-tract microbes are referred to as the gut microbiota. During the last ten years, our understanding of gut microbiota composition and its relation with intra- and extra-intestinal diseases including risk factors of cardiovascular diseases (CVD) such as atherosclerosis and metabolic syndrome, have greatly increased. A question which frequently arises in the research community is whether one can modulate the gut microbial environment to 'control' risk factors in CVD. In this review, we summarized promising intervention methods, based on our current knowledge of intestinal microbiota in modulating CVD. Furthermore, we explore how gut microbiota can be therapeutically exploited by targeting their metabolic program to control pathologic factors of CVD.

• Molecules and Cells
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• v.39 no.12
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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.

• Bulletin of the Korean Chemical Society
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• v.30 no.9
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• pp.2117-2120
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• 2009

• Toxicological Research
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• v.32 no.3
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• pp.177-193
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• 2016

After more than half of century since the Warburg effect was described, this atypical metabolism has been standing true for almost every type of cancer, exhibiting higher glycolysis and lactate metabolism and defective mitochondrial ATP production. This phenomenon had attracted many scientists to the problem of elucidating the mechanism of, and reason for, this effect. Several models based on oncogenic studies have been proposed, such as the accumulation of mitochondrial gene mutations, the switch from oxidative phosphorylation respiration to glycolysis, the enhancement of lactate metabolism, and the alteration of glycolytic genes. Whether the Warburg phenomenon is the consequence of genetic dysregulation in cancer or the cause of cancer remains unknown. Moreover, the exact reasons and physiological values of this peculiar metabolism in cancer remain unclear. Although there are some pharmacological compounds, such as 2-deoxy-D-glucose, dichloroacetic acid, and 3-bromopyruvate, therapeutic strategies, including diet, have been developed based on targeting the Warburg effect. In this review, we will revisit the Warburg effect to determine how much scientists currently understand about this phenomenon and how we can treat the cancer based on targeting metabolism.