Identification of a novel GLUT1 inhibitor with in vitro and in vivo anti-tumor activity

Chen, Xiaotong; Zhao, Yunshuo; He, Chuanjie; Gao, Guanmin; Li, Jiao; Qiu, Lu; Wang, Xiaoxi; Gao, Yanfeng; Qi, Yuanming; Sun, Kai; Du, Jiangfeng

doi:10.1016/j.ijbiomac.2022.07.123

Cited by 16 publications

(7 citation statements)

References 38 publications

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“…The small molecule SMI277 was identified as a novel GLUT1 inhibitor recently. SMI277 inhibited glucose uptake, decreased lactate secretion, and induced apoptosis in tumor cells [ 239 ]. Siebeneicher et al in 2016 employed HTS to identify novel 1H-pyrazolo[3,4-d]pyrimidines as novel GLUT inhibitors.…”

Section: Pharmacological Targetsmentioning

confidence: 99%

The Role of Reprogrammed Glucose Metabolism in Cancer

Ediriweera

Jayasena

2023

Metabolites

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Cancer cells reprogram their metabolism to meet biosynthetic needs and to adapt to various microenvironments. Accelerated glycolysis offers proliferative benefits for malignant cells by generating glycolytic products that move into branched pathways to synthesize proteins, fatty acids, nucleotides, and lipids. Notably, reprogrammed glucose metabolism and its associated events support the hallmark features of cancer such as sustained cell proliferation, hijacked apoptosis, invasion, metastasis, and angiogenesis. Overproduced enzymes involved in the committed steps of glycolysis (hexokinase, phosphofructokinase-1, and pyruvate kinase) are promising pharmacological targets for cancer therapeutics. In this review, we summarize the role of reprogrammed glucose metabolism in cancer cells and how it can be manipulated for anti-cancer strategies.

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Section: Pharmacological Targetsmentioning

confidence: 99%

The Role of Reprogrammed Glucose Metabolism in Cancer

Ediriweera

Jayasena

2023

Metabolites

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“…In the work of Chen et al [562], owing to comprehensive in vitro and in vivo analyses of the antitumor properties of SMI 277-a new modulator of GLUT1-the authors were able to detect the high inhibitory ability of the compound in relation to the process of glucose uptake, which was confirmed by a decrease in lactate production. This mechanism of action of SMI277 effectively inhibited proliferation and triggered the apoptotic death of the transformed cells, which, in in vivo experiments in a mouse model, was accompanied by a decrease in tumor size by more than 50%.…”

Section: Determination Of the Main Metabolic Processes Of The Cell An...mentioning

confidence: 99%

Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases

Aleksandrova,

Neganova

2023

IJMS

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The relationship between oncological pathologies and neurodegenerative disorders is extremely complex and is a topic of concern among a growing number of researchers around the world. In recent years, convincing scientific evidence has accumulated that indicates the contribution of a number of etiological factors and pathophysiological processes to the pathogenesis of these two fundamentally different diseases, thus demonstrating an intriguing relationship between oncology and neurodegeneration. In this review, we establish the general links between three intersecting aspects of oncological pathologies and neurodegenerative disorders, i.e., oxidative stress, epigenetic dysregulation, and metabolic dysfunction, examining each process in detail to establish an unusual epidemiological relationship. We also focus on reviewing the current trends in the research and the clinical application of the most promising chemical structures and therapeutic platforms that have a modulating effect on the above processes. Thus, our comprehensive analysis of the set of molecular determinants that have obvious cross-functional pathways in the pathogenesis of oncological and neurodegenerative diseases can help in the creation of advanced diagnostic tools and in the development of innovative pharmacological strategies.

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“…4 GLUT1 inhibition induces glucose deprivation, suppresses tumor cell growth, and causes tumor damage. 5,6 Thus, GLUT1 is a promising target for the treatment of tumors. 7 Many studies have sought new GLUT1 inhibitors as leads for creating innovative antitumor drugs.…”

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confidence: 99%

“…7 Many studies have sought new GLUT1 inhibitors as leads for creating innovative antitumor drugs. 6,8 However, few naturally sourced GLUT1 inhibitors have been studied, the majority of which are flavonoids. 9−11 It is essential to discover new GLUT1 inhibitors with novel scaffolds.…”

mentioning

confidence: 99%

“…GLUT1 is overexpressed in various tumor cell lines, especially in triple-negative breast cancer, where it mediates glucose uptake for energy production and biomass synthesis . GLUT1 inhibition induces glucose deprivation, suppresses tumor cell growth, and causes tumor damage. , Thus, GLUT1 is a promising target for the treatment of tumors . Many studies have sought new GLUT1 inhibitors as leads for creating innovative antitumor drugs. , However, few naturally sourced GLUT1 inhibitors have been studied, the majority of which are flavonoids. − It is essential to discover new GLUT1 inhibitors with novel scaffolds.…”

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confidence: 99%

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Target Separation and Potential Anticancer Activity of Withanolide-Based Glucose Transporter Protein 1 Inhibitors from Physalis angulata var. villosa

Zhang,

Xu,

Zhao

et al. 2023

J. Nat. Prod.

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The glucose transporter 1 (GLUT1) protein is involved in the basal-level absorption of glucose in tumor cells. Inhibiting GLUT1 decreases tumor cell proliferation and induces tumor cell damage. Natural GLUT1 inhibitors have been studied only to a small extent, and the structures of known natural GLUT1 inhibitors are limited to a few classes of natural products. Therefore, discovering and researching other natural GLUT1 inhibitors with novel scaffolds are essential. Physalis angulata L. var. villosa is a plant known as Mao-Ku-Zhi (MKZ). Withanolides are the main phytochemical components of MKZ. MKZ extracts and the components of MKZ exhibited antitumor activity in recent pharmacological studies. However, the antitumor-active components of MKZ and their molecular mechanisms remain unknown. A cell membrane-biomimetic nanoplatform (CM@Fe 3 O 4 /MIL-101) was used for target separation of potential GLUT1 inhibitors from MKZ. A new withanolide, physagulide Y (2), together with six known withanolides (1, 3−7), was identified as a potential GLUT1 inhibitor. Physagulide Y was the most potent GLUT1 inhibitor, and its antitumor activity and possible mechanism of action were explored in MCF-7 human cancer cells. These findings advance the development of technologies for the targeted separation of natural products and identify a new molecular framework for the investigation of natural GLUT1 inhibitors.

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Identification of a novel GLUT1 inhibitor with in vitro and in vivo anti-tumor activity

Cited by 16 publications

References 38 publications

The Role of Reprogrammed Glucose Metabolism in Cancer

The Role of Reprogrammed Glucose Metabolism in Cancer

Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases

Target Separation and Potential Anticancer Activity of Withanolide-Based Glucose Transporter Protein 1 Inhibitors from Physalis angulata var. villosa

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