scholarly journals Glucose Transporters as a Target for Anticancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4184
Author(s):  
Monika Pliszka ◽  
Leszek Szablewski
Keyword(s):  
Cancer Cells ◽  
Cancer Metabolism ◽  
Radioiodine Therapy ◽  
Hypoxic Condition ◽  
Glucose Transporters ◽  
Anticancer Therapy ◽  
Diagnostic Techniques ◽  
Normal Cells ◽  
Patients With Cancer ◽  
Oxidative Breakdown

Tumor growth causes cancer cells to become hypoxic. A hypoxic condition is a hallmark of cancer. Metabolism of cancer cells differs from metabolism of normal cells. Cancer cells prefer the process of glycolysis as a source of ATP. Process of glycolysis generates only two molecules of ATP per one molecule of glucose, whereas the complete oxidative breakdown of one molecule of glucose yields 36 molecules of ATP. Therefore, cancer cells need more molecules of glucose in comparison with normal cells. Increased uptake of glucose by these cells is due to overexpression of glucose transporters, especially GLUT1 and GLUT3, that are hypoxia responsive, as well as other glucose transport proteins. Increased expression of these carrier proteins may be used in anticancer therapy. This phenomenon is used in diagnostic techniques such as FDG-PET. It is also suggested, and there are observations, that therapeutic inhibition of glucose transporters may be a method in treatment of cancer patients. On the other hand, there are described cases, in which upregulation of glucose transporters, as, for example, NIS, which is used in radioiodine therapy, can help patients with cancer. The aim of this review is the presentation of possibilities, and how glucose transporters can be used in anticancer therapy.

scholarly journals Macrosphelide A Exhibits a Specific Anti-Cancer Effect by Simultaneously Inactivating ENO1, ALDOA, and FH

2021 ◽  
Vol 14 (10) ◽  
pp. 1060
Author(s):  
Kyoung Song ◽  
Nirmal Rajasekaran ◽  
Chaithanya Chelakkot ◽  
Hunseok Lee ◽  
Seungmann Paek ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Warburg Effect ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Fumarate Hydratase ◽  
Metabolic Adaptation ◽  
Normal Cells ◽  
Target Proteins ◽  
Anti Cancer ◽  
The Warburg Effect

Aerobic glycolysis in cancer cells, also known as the Warburg effect, is an indispensable hallmark of cancer. This metabolic adaptation of cancer cells makes them remarkably different from normal cells; thus, inhibiting aerobic glycolysis is an attractive strategy to specifically target tumor cells while sparing normal cells. Macrosphelide A (MSPA), an organic small molecule, is a potential lead compound for the design of anti-cancer drugs. However, its role in modulating cancer metabolism remains poorly understood. MSPA target proteins were screened using mass spectrometry proteomics combined with affinity chromatography. Direct and specific interactions of MSPA with its candidate target proteins were confirmed by in vitro binding assays, competition assays, and simulation modeling. The siRNA-based knockdown of MSPA target proteins indirectly confirmed the cytotoxic effect of MSPA in HepG2 and MCF-7 cancer cells. In addition, we showed that MSPA treatment in the HEPG2 cell line significantly reduced glucose consumption and lactate release. MSPA also inhibited cancer cell proliferation and induced apoptosis by inhibiting critical enzymes involved in the Warburg effect: aldolase A (ALDOA), enolase 1 (ENO1), and fumarate hydratase (FH). Among these enzymes, the purified ENO1 inhibitory potency of MSPA was further confirmed to demonstrate the direct inhibition of enzyme activity to exclude indirect/secondary factors. In summary, MSPA exhibits anti-cancer effects by simultaneously targeting ENO1, ALDOA, and FH.

scholarly journals CONCEPTUAL STUDY ON THE EFFECT OF MOORVADI CHOORNAM IN POST CHEMOTHERAPY COMPLICATIONS

2021 ◽  
pp. 79-83
Author(s):  
Aswathi G ◽  
C.K.Krishnan Nair ◽  
Prasanth S.R ◽  
Jayakrishnan P.G
Keyword(s):  
Survival Rate ◽  
Side Effects ◽  
Cancer Cells ◽  
Main Tool ◽  
Life Time ◽  
Normal Cells ◽  
Patients With Cancer ◽  
The World ◽  
Conceptual Study ◽  
Loss Of Appetite

Cancer, a disease which has enormously multiplied over a last few decades, put to suffer tens of millions of people all over the world irrespective of gender, age or colour. The incidence of patients with cancer in India among males was 94.1 per 100,000 and among females 103.6 per 100,000 in the year 2020. 1 in 9 Indians develop cancer during their life time. Now days, the survival rate of cancer is much better due to vigorous interventions. Chemotherapy, is one of the main tool to kill the rapidly growing cancer cells. i.e., it shows its poisonous effect or simply they are poisons. The effect of chemo drugs on normal cells often causes many side effects. In fact the administration of chemo drugs results in the accumulation of poisons that shows symptoms like hair fall, mouth sores, fatigue, loss of appetite etc. Many complications develop after chemotherapy due to Dhatuagnimandya occurring as a result of the accumulation of Garavisha (artificial poison). Most of the complications noticed are similar to Garavisha lakshanas such as Pandu, Alpagni, Durbalatha etc. Acharya mentioned the yoga “Moorvadichoornam” with proper Anupana, which is specified for indigestion due to Garavisha consisting of drugs with many properties to compensate the side effect of chemotherapy. In this paper, a conceptual study is proposed to evaluate the effect of Moorvadi choornam in post chemotherapeutic complications. Signs of Agnimandya is very clear at the level of Dhatus and this drug combination is expected to act at Jadaragni and Dhatuagni level.

scholarly journals Significance of low-carbohydrate diets and fasting in patients with cancer

2019 ◽  
pp. 325-336
Keyword(s):  
Growth Factors ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Standard Treatment ◽  
The Other ◽  
Normal Cells ◽  
Tumor Mass ◽  
Patients With Cancer ◽  
Low Carbohydrate ◽  
The Relationship

The differences between the metabolism and the physiology of cancer cells and the cells of the human body are assessed and used in most anticancer treatments. These differences encompass, among others, increased glucose metabolism in the changed cells. The aim of the paper was to discuss the results of studies concerning the relationship between lowcarbohydrate diets and fasting and the course of cancer. An inappropriately composed diet consisting of high amounts of simple sugars supplies cancer cells with nutrients, which may impair the effectiveness of cancer patients treatment. Lowcarbohydrate diets may, therefore, constitute an element of supplementary therapy in cancer treatment. The mechanism of low-carbohydrate diets in combination with standard treatment has not been completely explained, though. In initial studies it was proven that patients who were able to continue low-carbohydrate diets showed improvement in health and reduction of tumor mass or its slower growth. Moreover, it was observed that the inability of cancer cells to adapt in new environmental conditions that occur while fasting may have toxic effect on them. Introduction of fasting may sensitize cancer cells to chemotherapy, decrease concentration of growth factors and lead to repair of normal cells. On the other hand, fasting may also promote autophagy and, as can be concluded from the literature, its mechanism may have twofold activity: as a process impacting the survival or death of cancer cells.

scholarly journals More Than Meets the Eye Regarding Cancer Metabolism

2021 ◽  
Vol 22 (17) ◽  
pp. 9507
Author(s):  
Anna Kubicka ◽  
Karolina Matczak ◽  
Magdalena Łabieniec-Watała
Keyword(s):  
Cancer Cells ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Cancer Therapies ◽  
High Demand ◽  
Normal Cells ◽  
Regulatory Changes ◽  
The Difference ◽  
New Treatment ◽  
Atp Supply

In spite of the continuous improvement in our knowledge of the nature of cancer, the causes of its formation and the development of new treatment methods, our knowledge is still incomplete. A key issue is the difference in metabolism between normal and cancer cells. The features that distinguish cancer cells from normal cells are the increased proliferation and abnormal differentiation and maturation of these cells, which are due to regulatory changes in the emerging tumour. Normal cells use oxidative phosphorylation (OXPHOS) in the mitochondrion as a major source of energy during division. During OXPHOS, there are 36 ATP molecules produced from one molecule of glucose, in contrast to glycolysis which provides an ATP supply of only two molecules. Although aerobic glucose metabolism is more efficient, metabolism based on intensive glycolysis provides intermediate metabolites necessary for the synthesis of nucleic acids, proteins and lipids, which are in constant high demand due to the intense cell division in cancer. This is the main reason why the cancer cell does not “give up” on glycolysis despite the high demand for energy in the form of ATP. One of the evolving trends in the development of anti-cancer therapies is to exploit differences in the metabolism of normal cells and cancer cells. Currently constructed therapies, based on cell metabolism, focus on the attempt to reprogram the metabolic pathways of the cell in such a manner that it becomes possible to stop unrestrained proliferation.

scholarly journals The emerging role of targeting cancer metabolism for cancer therapy

Tumor Biology ◽  
2020 ◽  
Vol 42 (10) ◽  
pp. 101042832096528
Author(s):  
Pegah Farhadi ◽  
Reza Yarani ◽  
Sadat Dokaneheifard ◽  
Kamran Mansouri
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Pentose Phosphate ◽  
The Body ◽  
Acid Oxidation ◽  
Normal Cells ◽  
Cancer Hallmarks ◽  
Pentose Phosphate Pathways

Glucose, as the main consuming nutrient of the body, faces different destinies in cancer cells. Glycolysis, oxidative phosphorylation, and pentose phosphate pathways produce different glucose-derived metabolites and thus affect cells’ bioenergetics differently. Tumor cells’ dependency to aerobic glycolysis and other cancer-specific metabolism changes are known as the cancer hallmarks, distinct cancer cells from normal cells. Therefore, these tumor-specific characteristics receive the limelight as targets for cancer therapy. Glutamine, serine, and fatty acid oxidation together with 5-lipoxygenase are main pathways that have attracted lots of attention for cancer therapy. In this review, we not only discuss different tumor metabolism aspects but also discuss the metabolism roles in the promotion of cancer cells at different stages and their difference with normal cells. Besides, we dissect the inhibitors potential in blocking the main metabolic pathways to introduce the effective and non-effective inhibitors in the field.

Molecular Studies on Novel Antitumor Bis 1,4-Dihydropyridine Derivatives Against Lung Carcinoma and their Limited Side Effects on Normal Melanocytes

2019 ◽  
Vol 18 (15) ◽  
pp. 2156-2168 ◽  
Author(s):  
Magda F. Mohamed ◽  
Nada S. Ibrahim ◽  
Ahmed H.M. Elwahy ◽  
Ismail A. Abdelhamid
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Cell Line ◽  
Lung Carcinoma ◽  
Carcinoma Cell ◽  
Normal Cells ◽  
Lung Carcinoma Cell Line ◽  
Molecular Studies ◽  
Dihydropyridine Derivatives

Background: Cancer is a complex genetic disease which is characterized by an abnormal cell growth, invasion and spreading to other parts of the body. There are several factors that lead to cancer by causing DNA damage and the impairment of its repair. Treatment of cancer using the chemotherapeutic drugs have adverse side effects such as toxicity as they lose their specificity toward cancer cells and affect also normal cells. Moreover, the cancer cells can resist the chemotherapeutic agents and make them ineffective. For these reasons, much attentions have been paid to develop new drugs with limited side effects on normal cells and to diminish cancer resistance to drug chemotherapy. Recently, some 1,4-dihydropyridine derivatives were reported to act as Multi-Drug Resistance (MDR) modulators that inhibit p-glycoprotein which is responsible for the inability of drugs to enter the cancer cells. Also 1,4-DHPs have antimutagenic properties against chemicals via modulating DNA repair when studied on drosophila. Objective: The objective of this study is the synthesis of bis 1,4-DHPs incorporating ester as well as ether linkages and evaluate the anticancer activity of new compounds for synergistic purpose. Different genetic tools were used in an attempt to know the mechanism of action of this compound against lung cancer. Method: An efficient one pot synthesis of bis 1,4-DHPs using 3-aminocrotononitrile and bis(aldehydes) has been developed. The cytotoxic effect against human cell lines MCF7, and A549 cell lines was evaluated. Results: All compounds exhibited better cytotoxicity toward lung carcinoma cells than breast cancer cells. With respect to lung carcinoma cell line (A549), compound 10 was the most active compound and the three other compounds 7, 8, and 9 showed comparable IC50 values. In case of breast cancer cell line (MCF7), the most active one was compound 7, while compound 8 recorded the least activity. Conclusion: we have developed an efficient method for the synthesis of novel bis 1,4-dihydropyridine derivatives incorporating ester or ether linkage. All compounds showed better cytotoxicity results against A549 than MCF7, so that lung carcinoma cell line was chosen to perform the molecular studies on it. The results showed that all compounds (7, 8, 9 and 10) caused cell cycle arrest at G1 phase. The molecular docking study on CDK2 confirmed the results of cell cycle assay which showed good binding energy between the compounds and the active site of enzyme indicating the inhibition of the enzyme.

The Engaged Role of Tumor Microenvironment in Cancer Metabolism: Focusing on Cancer-Associated Fibroblast and Exosome Mediators

2020 ◽  
Vol 21 (2) ◽  
pp. 254-266 ◽  
Author(s):  
Khandan Ilkhani ◽  
Milad Bastami ◽  
Soheila Delgir ◽  
Asma Safi ◽  
Shahrzad Talebian ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Krebs Cycle ◽  
Metabolic Reprogramming ◽  
Cancer Management ◽  
Cancer Associated Fibroblast ◽  
Potential Biomarker ◽  
Close Relationship ◽  
Microenvironmental Factors

: Metabolic reprogramming is a significant property of various cancer cells, which most commonly arises from the Tumor Microenvironment (TME). The events of metabolic pathways include the Warburg effect, shifting in Krebs cycle metabolites, and the rate of oxidative phosphorylation, potentially providing energy and structural requirements for the development and invasiveness of cancer cells. TME and tumor metabolism shifting have a close relationship through bidirectional signaling pathways between stromal and tumor cells. Cancer- Associated Fibroblasts (CAFs), as the most dominant cells of TME, play a crucial role in the aberrant metabolism of cancer. Furthermore, the stated relationship can affect survival, progression, and metastasis in cancer development. Recently, exosomes are considered one of the most prominent factors in cellular communications considering effective content and bidirectional mediatory effect between tumor and stromal cells. In this regard, CAF-Derived Exosomes (CDE) exhibit an efficient obligation to induce metabolic reprogramming for promoting growth and metastasis of cancer cells. The understanding of cancer metabolism, including factors related to TME, could lead to the discovery of a potential biomarker for diagnostic and therapeutic approaches in cancer management. This review focuses on the association between metabolic reprogramming and engaged microenvironmental, factors such as CAFs, and the associated derived exosomes.

scholarly journals Hemistepsin A suppresses colorectal cancer growth through inhibiting pyruvate dehydrogenase kinase activity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ling Jin ◽  
Eun-Yeong Kim ◽  
Tae-Wook Chung ◽  
Chang Woo Han ◽  
So Young Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Pyruvate Dehydrogenase Kinase ◽  
Cancer Drug ◽  
Potential Candidate ◽  
Mitochondrial Ros

AbstractMost cancer cells primarily produce their energy through a high rate of glycolysis followed by lactic acid fermentation even in the presence of abundant oxygen. Pyruvate dehydrogenase kinase (PDK) 1, an enzyme responsible for aerobic glycolysis via phosphorylating and inactivating pyruvate dehydrogenase (PDH) complex, is commonly overexpressed in tumors and recognized as a therapeutic target in colorectal cancer. Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata Bunge (Compositae). Here, we report that HsA is a PDK1 inhibitor can reduce the growth of colorectal cancer and consequent activation of mitochondrial ROS-dependent apoptotic pathway both in vivo and in vitro. Computational simulation and biochemical assays showed that HsA directly binds to the lipoamide-binding site of PDK1, and subsequently inhibits the interaction of PDK1 with the E2 subunit of PDH complex. As a result of PDK1 inhibition, lactate production was decreased, but oxygen consumption was increased. Mitochondrial ROS levels and mitochondrial damage were also increased. Consistent with these observations, the apoptosis of colorectal cancer cells was promoted by HsA with enhanced activation of caspase-3 and -9. These results suggested that HsA might be a potential candidate for developing a novel anti-cancer drug through suppressing cancer metabolism.

scholarly journals Normal cells repel WWOX-negative or -dysfunctional cancer cells via WWOX cell surface epitope 286-299

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yu-An Chen ◽  
Yong-Da Sie ◽  
Tsung-Yun Liu ◽  
Hsiang-Ling Kuo ◽  
Pei-Yi Chou ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cancer Cells ◽  
Room Temperature ◽  
Metastatic Cancer ◽  
Normal Cells ◽  
Tgfβ Receptor ◽  
Membrane Type ◽  
Cell Invasiveness ◽  
And Control ◽  
Metastatic Cancer Cells

AbstractMetastatic cancer cells are frequently deficient in WWOX protein or express dysfunctional WWOX (designated WWOXd). Here, we determined that functional WWOX-expressing (WWOXf) cells migrate collectively and expel the individually migrating WWOXd cells. For return, WWOXd cells induces apoptosis of WWOXf cells from a remote distance. Survival of WWOXd from the cell-to-cell encounter is due to activation of the survival IκBα/ERK/WWOX signaling. Mechanistically, cell surface epitope WWOX286-299 (repl) in WWOXf repels the invading WWOXd to undergo retrograde migration. However, when epitope WWOX7-21 (gre) is exposed, WWOXf greets WWOXd to migrate forward for merge. WWOX binds membrane type II TGFβ receptor (TβRII), and TβRII IgG-pretreated WWOXf greet WWOXd to migrate forward and merge with each other. In contrast, TβRII IgG-pretreated WWOXd loses recognition by WWOXf, and WWOXf mediates apoptosis of WWOXd. The observatons suggest that normal cells can be activated to attack metastatic cancer cells. WWOXd cells are less efficient in generating Ca2+ influx and undergo non-apoptotic explosion in response to UV irradiation in room temperature. WWOXf cells exhibit bubbling cell death and Ca2+ influx effectively caused by UV or apoptotic stress. Together, membrane WWOX/TβRII complex is needed for cell-to-cell recognition, maintaining the efficacy of Ca2+ influx, and control of cell invasiveness.

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