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ObjectiveTo analyze the expression of Lactate dehydrogenase A（LDHA） in both renal cell carcinoma （RCC） tissue and RCC cell lines， and to investigate the impact of LDHA expression on the progression of RCC. MethodsFrom June 2018 to June 2022， totally 52 cases of RCC tissue samples and 49 cases of para-cancerous tissue samples were collected through surgical procedures from our hospital. LDHA expression was detected using immunohistochemistry （IHC）. The expression levels of LDHA in vitro were also detected in the normal human proximal tubule epithelial cell line HK-2 and renal cell carcinoma cell lines A498， Caki-2， ACHN， and 786-O by using qRT-PCR and Western blot. A recombinant plasmid carrying LDHA-shRNA was constructed and then transfected into 786-O cells to down-regulate the expression of LDHA. Tumor proliferative capacity was monitored using CCK-8 assay， clonal formation assay and EdU assessments. Additionally， cell glycolytic activity was assessed through glucose uptake assay， lactate secretion assay， and ECAR analysis. ResultsIHC analysis revealed significantly higher expression of LDHA in RCC tissue compared to adjacent tissues（P<0.05）. Furthermore， RCC tissues with higher TNM stage exhibited greater expression of LDHA than those with lower TNM stage （P<0.05）. The results of qRT-PCR and Western blot demonstrated that the expression of LDHA in each RCC cell line was significantly higher than that in HK-2（P<0.05）. After blocking the expression of LDHA in 786-O， there was a significant down-regulation of cell proliferation and glycolysis capacity （P<0.05）. ConclusionsThe expression of LDHA in RCC tissue and RCC cell lines is significantly overexpressed compared with normal one， particularly in those with higher TNM stage. Knockdown of the expression of LDHA significantly suppresses cell proliferation and aerobic glycolysis capacity in 786-O.
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Abstract Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. Objectives This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. Methodology OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. Results CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. Conclusion OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.
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One of the distinct hallmarks of cancer cells is aerobic glycolysis (Warburg effect). Lactate dehydrogenase A (LDHA) is thought to play a key role in aerobic glycolysis and has been extensively studied, while lactate dehydrogenase C (LDHC), an isoform of LDHA, has received much less attention. Here we showed that human LDHC was significantly expressed in lung cancer tissues, overexpression of Ldhc in mice could promote tumor growth, and knock-down of LDHC could inhibit the proliferation of lung cancer A549 cells. We solved the first crystal structure of human LDHC4 and found that the active-site loop of LDHC4 adopted a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Moreover, we found that (ethylamino) (oxo)acetic acid shows about 10 times selective inhibition against LDHC4 over LDHA4 and LDHB4. Our studies suggest that LDHC4 is a potential target for anticancer drug discovery and (ethylamino) (oxo)acetic acid provides a good start to develop lead compounds for selective drugs targeting LDHC4.
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Radiotherapy is an important auxiliary treatment for glioma. Although comprehensive treatment of glioma has made some progress in recent years, the prognosis is still poor. How to improve the radiosensitivity of glioma is one of the hot spots in current glioma research. The changes of energy metabolism in gliomas promote malignant progression and resistance to chemoradiotherapy, but the exact mechanism is still unclear. This paper reviews the research progress of energy metabolism in gliomas and its relation with radiosensitivity of gliomas, in order to lay a foundation for further exploration of improving radiosensitivity of gliomas.
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Retinal metabolism includes material metabolism and energetic metabolism.Retina is one of the most energy-consuming nerve tissue in human body and mainly relies on glycolysis for energy production, which is similar to very fast-growing tumor tissue.This process is known as Warburg effect.Warburg effect is of great significance, which is demonstrated that glucose is metabolized via glycolysis in a more rapid approach in comparison with oxidative phosphorylation pathway.In addition, glucose also supplies neoplastic tissue with carbon source or metabolic intermediates due to biosynthesis.The produced energy of retina is a summation of different retinal cells and tissue, such as photoreceptors, retinal pigment epithelium (RPE), Müller cells and retinal capillary endothelial cells etc.To understand the underlying mechanism contributing to Warburg effect and provide insight into metabolic coupling between neuron and glia is of important significance.Since key glycolysis enzymes (HK2, PFKFB3 and PKM2) take a pivotal role in controlling retinal cell proliferation and neovascularization, bioenergetic strategy targeting these enzymes suggests new idea in the treatment of retinal diseases where energy failure is part of the pathogenesis.Investigating underlying mechanism of retinal energy metabolism can provide new ideas for the treatment of age-related macular degeneration (AMD) and other diseases related to disordered retinal energy metabolism.The Warburg effect of retinal energetic metabolism and its regulatory mechanism were reviewed in this article.
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Solid tumors are complex entities, comprising a wide variety of malignancies with very different molecular alterations. Despite this, they share a set of characteristics known as "hallmarks of cancer" that can be used as common therapeutic targets. Thus, every tumor needs to change its metabolism in order to obtain the energy levels required for its high proliferative rates, and these adaptations lead to alterations in extra- and intracellular pH. These changes in pH are common to all solid tumors, and can be used either as therapeutic targets, blocking the cell proton transporters and reversing the pH changes, or as means to specifically deliver anticancer drugs. In this review we will describe how proton transport inhibitors in association with nanocarriers have been designed to block the pH changes that are needed for cancer cells to survive after their metabolic adaptations. We will also describe studies aiming to decrease intracellular pH in cancer using nanoparticles as molecular cages for protons which will be released upon UV or IR light exposure. Finally, we will comment on several studies that have used the extracellular pH in cancer for an enhanced cell internalization and tumor penetration of nanocarriers and a controlled drug delivery, describing how nanocarriers are being used to increase drug stability and specificity.
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Background: According to Darwin's theory of evolution, complex creatures evolve from more simplistic ancestors. Dollo's law of irreversibility states that evolution is irreversible. However, cancer cells tend to follow anti-Dollo's law. Unfavorable conditions such as hypoxia, acidic pH and low nutrients cause the cancer cells to switch their lifestyle atavistically in order to survive. They start behaving like a unicellular organism. There is a switch from normal metabolism to Warburg effect and finally cannibalism. Cannibalism is a cell eating cell phenomenon. It is defined as a large cell enclosing a smaller one within its cytoplasm and is known by odd names such as “bird's eye cells” or “signet ring cells.” Smaller tumor cells are found in the cytoplasm of larger tumor cells with crescent-shaped nucleus. Cannibalistic cells (CCs) are a feature of aggressive tumors. These cell types are vulnerable to metastasis. Aim: The aim of this study is to identify CCs in various histological grades of oral squamous cell carcinoma (OSCC) and to relate them with the pattern of invasion, lymphocytic response (LR), and mitotic figures (Mfs). The purpose of the article is to establish it as a marker of aggressiveness and metastasis and as an evidence of de-evolution and retroversion of multicellularity. Materials and Methods: Sixty-five histologically confirmed cases of OSCC were studied. Pattern of invasion, LR, number of CCs, and Mfs were recorded on 5 μ hematoxylin and eosin-stained tissue sections. ANOVA and t-test were applied; P < 0.05 was considered statistically significant. Results: CCs were more in sections with patchy LR, increased Mfs, and grade IV pattern of invasion. Conclusion: With increase in dedifferentiation, tumor cells start behaving like unicellular organisms with cell eating cell characteristics
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It has been observed that both cancer tissue cells and normal proliferating cells (NPCs) have the Warburg effect. Our goal here is to demonstrate that they do this for different reasons. To accomplish this, we have analyzed the transcriptomic data of over 7000 cancer and control tissues of 14 cancer types in TCGA and data of five NPC types in GEO. Our analyses reveal that NPCs accumulate large quantities of ATPs produced by the respiration process before starting the Warburg effect, to raise the intracellular pH from ∼6.8 to ∼7.2 and to prepare for cell division energetically. Once cell cycle starts, the cells start to rely on glycolysis for ATP generation followed by ATP hydrolysis and lactic acid release, to maintain the elevated intracellular pH as needed by cell division since together the three processes are pH neutral. The cells go back to the normal respiration-based ATP production once the cell division phase ends. In comparison, cancer cells have reached their intracellular pH at ∼7.4 from top down as multiple acid-loading transporters are up-regulated and most acid-extruding ones except for lactic acid exporters are repressed. Cancer cells use continuous glycolysis for ATP production as way to acidify the intracellular space since the lactic acid secretion is decoupled from glycolysis-based ATP generation and is pH balanced by increased expressions of acid-loading transporters. Co-expression analyses suggest that lactic acid secretion is regulated by external, non-pH related signals. Overall, our data strongly suggest that the two cell types have the Warburg effect for very different reasons.
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; Aim To culture primary human gastric cancer associated fibroblasts (CAFs) and normal fibroblasts (NFs), and to explore the biological characteristics and their effects on gastric cancer cells. Methods After isolation and culture of CAFs and NFs, growth curve was drawn by MTT. The a-smooth muscle actin (ot-SMA) and Vimentin were detected by Immunofluorescence, Western blot and qRT-PCR. MGC-803 cells were co-cultured with CAFs and NFs in Transwell suspension mode. The migration and invasion ability of gastric cancer cells was detected by Transwell. The proliferation activity and AMD3100 on CAFs-gastric cancer co-culture system were compared by MTT. The acidic property, lactic acid and ROS contents of co-culture system were determined by PH meter, lactic acid and DCFH-DA method. Results The morphology of CAFs, NFs cells were in long spindle or flat star shape. The proliferation ability and overlapping growth phenomenon of CAFs were higher than those of NFs. The expression of ct-SMA and Vimentin cells was positive in CAFs, but low or negative in NFs cells. The activity of gastric cancer in low density co-culture group > medium density group > high density group, the PH value of CAFs co-culture system decreased, the content of lactic acid and ROS was high, and only CAFs low density co-culture group had significant effect on promoting cancer. Conclusions The co-culture of gastric cancer cells with CAFs and NFs is greatly affected by the proportion. Low density co-culture can significantly improve the proliferation and metastasis ability of gastric cancer cells. High density co-culture may in turn inhibit the growth and metastasis of cancer cells, which may be related to the content of lactic acid and ROS.
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In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate which is used by oxygenated cancer cells. This study challenged the Warburg effect, because Warburg claimed that fermentation by irreversible damaging of mitochondria is a fundamental cause of cancer. However, recent studies revealed that mitochondria in cancer cell show active function of oxidative phosphorylation although TCA cycle is stalled. It was also shown that blocking cytosolic NADH production by aldehyde dehydrogenase inhibition, combined with oxidative phosphorylation inhibition, resulted in up to 80% decrease of ATP production, which resulted in a significant regression of tumor growth in the NSCLC model. This suggests a new theory that NADH production in the cytosol plays a key role of ATP production through the mitochondrial electron transport chain in cancer cells, while NADH production is mostly occupied inside mitochondria in normal cells.
Subject(s)
Adenosine Triphosphate , Aldehyde Dehydrogenase , Cytosol , Electron Transport , Energy Metabolism , Fermentation , Glucose , Lactic Acid , Metabolism , Mitochondria , NAD , Oxidative Phosphorylation , Oxygen , SymbiosisABSTRACT
Objective To study the radiosensitization of irisquinone on the Warburg effect of MDA-MB231 cells.Methods MDA-MB231 cells in the exponential growth phase were divided into 6 groups:control group,irisquinone group,radiation group,irisquinone plus radiation group(Irisquinone + RA),negative control group,and experimental group (siRNA).Colony formation assay was used to measure cell survival fraction of MDA-MB231 cells.Single-hit multi-target model was used to fit the survival curve and calculate the sensitive enhancement ratio (SER).Flow cytometry was used to measure cell apoptosis.The relative expression levels of HK Ⅱ mRNA and protein in each group were detected by qRT-PCR and Western blot respectively.Results The values of D0,Dq and SF2 in the irisquinone plus radiation group were obviously lower than those in the radiation group.The SER of irisquinone was 1.52.Compared with the other groups,the cell apoptosis rate was increased (t =13.29,12.09,5.90,3.83,P ＜ 0.05),while the relative expression levels of HK Ⅱ mRNA (t =9.14,10.48,3.40,P＜0.05) and protein (t=13.39,16.08,5.81,P ＜ 0.05) were decreased in the irisquinone plus radiation group significantly.Conclusions Radiosensitization function of irisquinone inhibits the Warburg effect of MDA-MB231 cells by down-regulating the expression of HK Ⅱ.
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The occurrence and development of tumor are closely related to abnormal cell metabolism.Tumor cells intake a large amount of glucose,and even with enough oxygen supply,they also generate energy primarily through the glycolysis pathway to meet the need of rapid growth.Tumor cell glycolysis is affected by many factors,and the tumor microenvironment is one of them.In re-cent years,there is evidence that immune/inflammatory factors such as transforming growth factor beta(TGF-β),tumor necrosis fac-tor alpha(TNF- α),interleukin-4(IL-4),and interleukin-6(IL-6)in the microenvironment matrix play a crucial role in the process of glucose metabolism,by regulating the aerobic glycolysis of energy and material to rapidly growth and proliferation of tumor cells.Therefore,the occurrence and development of tumor are focused on coming from the point of view of regulating the glycation of tumor cells with immune/inflammatory factors in the tumor microenvironment,providing new ideas for tumor control and clinical treat-ment.
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Objective To study the influence of long time exposure to low levels of sodium arsenite on Warburg effect in cultured human epithelial cells (SV-HUC-1) at different times.Methods SV-HUC-1 cells were exposed to 0.5 μmol/L sodium arsenite for 10,20,30 weeks and cells cultured without sodium arsenite for 10,20,30 weeks were regarded as control groupsin vitro.Lactate assay kit and glucose assay kit were used to measure the lactate secretion and glucose consumption levels,and cells mRNA and protein expressions of SCL2A1 and hexokinase2(HK2) were detected using Real-time PCR and Western blotting.Results The levels of lactate secretion [(4.67 ± 0.20),(7.47 ± 0.28),(12.46 + 0.47) mmol/L],glucose consumption [(2.86 ± 0.11),(4.25 ± 0.19),(6.38 ± 0.05) mmol/L] and expression of HK2 protein (1.21 ± 0.06,1.36 ± 0.13,1.60 ± 0.12) increased significantly after treated with 0.5 μmol/L sodium for 10,20,30 weeks compared with those of control groups [(3.04 ± 0.11),(3.90 ± 0.32),(4.77 ± 0.24) mmol/L;(2.17 ± 0.15),(2.48 ± 0.24),(2.71 ± 0.13) mmol/L;1.00 ± 0.00;P ＜ 0.05].Compared with control group,the expressions of SCL2A1 mRNA,HK2 mRNA and SCL2A1 protein in SV-HUC-1 cells treated with sodium arsenite for 10 weeks increased but the difference was not statistically significant (P ＞ 0.05).While the expressions of SCL2A1 mRNA,HK2 mRNA and SCL2A1 protein in SV-HUC-1 cells treated with sodium arsenite for 20 and 30 weeks increased significantly compared to those of control groups (P ＜ 0.05).Conclusion Long-term exposure to low concentrations of sodium arsenite can increase glycolysis in SV-HUC-1 and induce Warburg effect.
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AIM:To investigate the influence of signal transducer and activator of transcription 3(STAT3)on Warburg effect in the malignant transformation of WB-F344 rat hepatic oval cells.METHODS:The WB-F344 cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)and hydrogen peroxide(H2O2)to induce the malignant trans-formation.Evaluation of the transformed cells were measured by the soft agar colony formation assay and DNA aneuploidy with flow cytometry.The levels of glucose and lactate in the culture medium of the cells were detected by chromatography. The protein levels of alpha-fetoprotein(AFP),STAT3,p-STAT3 and glucose transporter 2(GLUT2)in the cells were ex-amined by Western blot analysis.The cell proliferation were evaluated by WST-1 assay,viable cell counting,measuring the S-phase fraction(SPF)and proliferation index(PI)using the data from flow cytometry analysis,and detecting proliferating cell nuclear antigen(PCNA)protein expression by Western blot.RESULTS:Compared with the control cells,the forma-tion of colonies in soft agar(P<0.05)and DNA aneuploidy(P<0.01)were elevated in transformed cells,and the ex-pression level of AFP was also augmented(P<0.05).The increases in the level of both glucose consumption(P<0.05) and lactate production(P<0.01)show that Warburg effect was enhanced in transformed cells.Meanwhile, the protein levels of GLUT2(P<0.01)and p-STAT3(P<0.01)in transformed cells were higher than those in the control cells.The cell proliferation parameters including SPF(P<0.01),PI(P<0.01), viable cell number and PCNA expression(P<0.01)in transformed cells were also elevated as compared with the control cells.Interestingly, stattic, an inhibitor of STAT3 activation,resulted in declines in glucose consumption(P<0.05)and lactate production(P<0.01)in the trans-formed cells.In addition,compared with transformed cells,formation of colonies in soft agar(P<0.01),DNA aneuploidy (P<0.01),AFP(P<0.05), GLUT2(P<0.05), and cell proliferation parameters including SPF(P<0.01), PI (P<0.01),viable cell number(P<0.05)and PCNA expression(P<0.05)were also decreased following stattic treat-ment in transformed cells.CONCLUSION:STAT3 promotes Warburg effect and cell proliferation probably by upregula-ting GLUT2 expression in the malignant transformation of hepatic oval cells.
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The growth of tumour cells is closely related to cancer-associated fibroblasts (CAFs)present within their microenvironment. CAFs, the most abundant cells in tumour stroma, secretegrowth factors that play pivotal roles in tumour cell proliferation, metabolism, angiogenesis andmetastasis. Tumour cells adapt to rapid environmental changes from normoxia to hypoxia throughmetabolic interplay with CAFs. In this mini review, we discuss the role of lactate dehydrogenases(LDHs) and monocarboxylate transporters (MCTs) on the metabolic interplay between tumourcells and CAFs under hypoxia compared to normoxia. The LDHs catalyse the interchange oflactate and pyruvate, whereas MCTs facilitate the influx and efflux of monocarboxylates, especiallylactate and pyruvate. To sum up, tumour cells switch their metabolic state between glycolysis andoxidative phosphorylation through metabolic interplay with CAFs, which exhibit the Warburgeffect under hypoxia and reverse Warburg effect under normoxia.
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Tumor cell energy metabolism is dependent on glycolysis and oxidative phosphorylation.Tumor cells,because of its rapid growth,often show increased intake of glucose and other nutrients,increased glycolysis and so on.In recent years,the study on energy metabolism of tumor cells has received extensive attention.This paper summarizes the required nutrients,regulatory networks and therapeutic targets in the energy metabolism of tumor cells,and provides important reference for future research and clinical treatment.
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OBJECTIVE To investigate the regulation of {O2 (2,4-dinitrophenyl)1-〔(4-ethoxycarbonyl) piperazin-1-yl〕diazen-1-ium-1,2-diolate}(JS-K), anitric oxide donor, on tumor energy metabolism in H22 tumor- bearing mice. METHODS The hepatoma animal model in BALB/c mice was established with H22 cell line. The JS-K group and model group were received JS-K (0.75 and 1.5 mg?kg-1) and saline via tail intravenous once every 3 d for 14 d, received 5 injections, respectively. The positive group was received 5-FU 20 mg·kg- 1 by intraperitoneal injection once a day for 14 d. On the 15th day mice were sacrificed. The tumor growth inhibition rate were calculated. The activities of hexokinase (HK), phospho?fructo kinase (PFK), pyruvate kinase (PK), succinate dehydrogenase (SDH), adenosine triphosphatase (ATPase), and the levels of lactic acid (LD) and adenosine triphosphate (ATP) in tumor tissues were de?termined by colorimetric method. RESULTS Compared with model group, the tumor mass of JS- K 0.75 and 1.5 mg·kg- 1group was significantly reduced (P<0.01),and the tumor growth inhibition rate was 23.9% and 50.3%, respectively. The activity of HK, PFK, PK, SDH and ATPase of tumor tissue in model group was (22.6±3.7, 14.4±2.6, 12.9±3.2 and 10.5±2.6)U·g-1 protein and (0.70±0.10)μmolPi·mg-1 protein per hour, respectively; which in JS-K 1.5 mg?kg-1 group was dropped by 42.0%, 26.6%, 22.7%, 23.3% and 21.7% (P<0.01, P<0.05). Compared with the model group, the level of ATP and LD in JS-K group was dropped (P<0.01). CONCLUSION JS-K can inhibit the growth of tumor in H22 tumor-bearing mice and its mechanism may be related to regulating the tumor energy metabolism with inhibition of glycolysis and aerobic oxidation.
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The present study aimed to research pathogenesis and therapeutics of hepatocellular carcinoma (HCC) with the method of tissue metabolomics.A combined gas chromatography-mass spectrometry (GC-MS) method was developed suitable for analyzing the endogenous small molecule of liver cancer tissues and adjacent tissues.The unidimensional and multidimensional statistics were used to look for differential metabolites.And then,the KEGG and HMDB database were utilized to find related differential pathways and pathogenesis of HCC.The PCA and PLS-DA showed that there were significant differences on the endogenous small molecule of liver cancer tissues and adjacent tissues.Through the OPLS-Loading plot analysis,there were 25 differential metabolites and 36 relevant pathways.The differential pathways belong to carbohydrate metabolism,amino acid metabolism and mitochondrial transfer.There were 16 metabolites' area under the ROC curve which was bigger than 0.8,which were related with ATP-binding cassette (ABC) transporters,galactose metabolism,amino sugar and nucleotide sugar metabolism.It was concluded that the Warburg effect exists in HCC cells.The energy of HCC cell was from glycolytic function,because the glycolysis was enhanced and the citric acid cycle decreased.Mitochondrial dysfunction and the increased cobalt content may correlate with the Warburg effect,which may be one of the pathogenesis of liver cancer,and expected to become the breakthrough point of a new targeting therapeutic approach.
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Tumor cells can escape from the normal apoptosis process and enhance the ability of proliferation and migration via an abnormal glucose metabolism.This abnormal glucose metabolism is named the Warburg effect,which plays a key role in the incidence of tumor.The Warburg effect is that,under aerobic condition,attenuating aerobic respiration of tumor cells via a series of molecular mechanisms,and exhibiting higher glycolysis metabolism and adenosine triphosphate (ATP) production,and meanwhile,creating the micro-environment that suitable for tumor cell survival,inducing proliferation advantages for tumor cells.In addition,the Warburg effect-induced regional hypoxia reduces monitoring effect and lethality of T-lymphocytes,and thus induces immune escape of tumor cells.By inhibiting related pathways of Warburg effect,some drugs such as 2-deoxy-D-glucose and dichloroacetic acid have effective ability to inhibit Warburg effect-caused proliferation advantages and immune escape of tumor cells,and thus inhibit tumor cells growth and promote tumor cells death.Moreover,health diet also effectively inhibits the Warburg effect.However,there are also some problems to be solved.As the development of researches on the Warburg effect,the effect of various antitumor drugs will be revalued,and these will provide new theoretical basis and research direction for tumor prevention and therapy.
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The glucose metabolism pathways including glycolysis and oxidative phosphorylation in vivo.The metabolism of tumor cells depends on glycolysis,which enhances the adaptability of tumor cells to the microenvironment and promotes the proliferation of tumor cells,which is called Warburg effect.Arsenic is one of the chemical pollutants,which is widely distributed in natural environment.International agency for research on cancer (IARC) has made it clear that arsenic and its compounds are carcinogens.However,the mechanism of carcinogenesis induced by arsenic still remains obscure.Recently,researchers have found that Warburg effect plays an important role in the process of arsenic carcinogenesis.In this paper,we have reviewed the definition and function of glycolysis,its relationship with inflammation and tumorigenesis,and the role of Warburg effect in arsenic carcinogenesis.