Pharmacological Ascorbate Suppresses Growth of Gastric Cancer Cells with GLUT1 Overexpression and Enhances the Efficacy of Oxaliplatin Through Redox Modulation

Lü, Yun; Wu, Qi; Chen, Dong Liang; Chen, Le Zong; Wang, Zi‐Xian; Ren, Chao; Mo, Hai Yu; Chen, Ya; Sheng, Hui; Wang, Ying Nan; Wang, Yun; Lu, Jia; Wang, De Shen; Zeng, Zhao Lei; Wang, Feng; Wang, Feng Hua; Li, Yu Hong; Ju, Huai-Qiang; Xu, Rui‐Hua

doi:10.7150/thno.21745

Cited by 52 publications

(34 citation statements)

References 47 publications

(90 reference statements)

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“…In some cases, there have been no benefits. However, new knowledge regarding the pharmacokinetic properties of Vit-C, and recent preclinical studies, have revived interest in the utilization of high-dose Vit-C for cancer treatment [132][133][134][135][136][137][138][139][140][141][142][143][144][145]. Similar is the case of using IV Vit-C as antiviral, especially for the recent Covid19 [146][147][148][149][150].…”

Section: Discussionmentioning

confidence: 99%

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome

2020

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Section: Discussionmentioning

confidence: 99%

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome

2020

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“…It is accepted that a diet rich in ascorbate has various health advantages (Wintergerst et al, 2006; Reczek and Chandel, 2015; Carr and Maggini, 2017; van Gorkom et al, 2018). Furthermore, in the last few years, ascorbate has been proposed as a treatment against different types of cancer through various mechanisms, such as increasing TET’s activity, inducing oxidative stress in cancer cells or enhancing the activity of various chemical treatments (Ko et al, 2015; Yun et al, 2015; Agathocleous et al, 2017; Cimmino et al, 2017; Shenoy et al, 2017; Lu et al, 2018; Miura et al, 2018). Daily intake of ascorbate provided by fruits is dependent on several factors, but clearly the content of ascorbate as well as the amount that is consumed are the most important factors.…”

Section: Major Fruit Supplies Of Ascorbate In Humansmentioning

confidence: 99%

Vitamin C Content in Fruits: Biosynthesis and Regulation

et al. 2019

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Throughout evolution, a number of animals including humans have lost the ability to synthesize ascorbic acid (ascorbate, vitamin C), an essential molecule in the physiology of animals and plants. In addition to its main role as an antioxidant and cofactor in redox reactions, recent reports have shown an important role of ascorbate in the activation of epigenetic mechanisms controlling cell differentiation, dysregulation of which can lead to the development of certain types of cancer. Although fruits and vegetables constitute the main source of ascorbate in the human diet, rising its content has not been a major breeding goal, despite the large inter- and intraspecific variation in ascorbate content in fruit crops. Nowadays, there is an increasing interest to boost ascorbate content, not only to improve fruit quality but also to generate crops with elevated stress tolerance. Several attempts to increase ascorbate in fruits have achieved fairly good results but, in some cases, detrimental effects in fruit development also occur, likely due to the interaction between the biosynthesis of ascorbate and components of the cell wall. Plants synthesize ascorbate de novo mainly through the Smirnoff-Wheeler pathway, the dominant pathway in photosynthetic tissues. Two intermediates of the Smirnoff-Wheeler pathway, GDP-D-mannose and GDP-L-galactose, are also precursors of the non-cellulosic components of the plant cell wall. Therefore, a better understanding of ascorbate biosynthesis and regulation is essential for generation of improved fruits without developmental side effects. This is likely to involve a yet unknown tight regulation enabling plant growth and development, without impairing the cell redox state modulated by ascorbate pool. In certain fruits and developmental conditions, an alternative pathway from D-galacturonate might be also relevant. We here review the regulation of ascorbate synthesis, its close connection with the cell wall, as well as different strategies to increase its content in plants, with a special focus on fruits.

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“…Suppressing GLUT1 and HKII inhibits the activity of glycolysis and induces cell apoptosis [21,[29][30][31]. Moreover, the inactivation of the AKT-GLUTI/HKII signaling pathway suppressed the proliferation and glycolysis of lung cancer cells [32].…”

Section: Discussionmentioning

confidence: 99%

TRIM32 Promotes the Growth of Gastric Cancer Cells through Enhancing AKT Activity and Glucose Transportation

Wang

Fang

Liu

2020

BioMed Research International

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Tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, is a member of the TRIM protein family. However, the underlying function of TRIM32 in gastric cancer (GC) remains unclear. Here, we aimed to explore the function of TRIM32 in GC cells. TRIM32 was induced silencing and overexpression using RNA interference (RNAi) and lentiviral-mediate vector in GC cells, respectively. Moreover, the PI3K/AKT inhibitor LY294002 was used to examine the relationship between TRIM32 and AKT. Quantitative reverse-transcription PCR (qRT-PCR) and western blot were used to determine the mRNA and protein contents. The glucose analog 2-NBDG was used as a fluorescent probe for determining the activity of glucose transport. An annexin V-fluorescein isothiocyanate apoptosis detection kit was used to stain NCI-N87, MKN74, and MKN45 cells. Cell counting kit-8 (CCK-8) assay was used to examine cell proliferation. Our results indicated that TRIM32 was associated with poor overall survival of patients with GC. Moreover, TRIM32 was a proproliferation and antiapoptosis factor and involved in the AKT pathway in GC cells. Furthermore, TRIM32 possibly mediated the metabolism of glycolysis through targeting GLUT1 and HKII in GC cells. Importantly, TRIM32 silencing deeply suppressed the tumorigenicity of GC cells in vivo. Our findings not only enhanced the understanding of the function of TRIM32 but also indicated its potential value as a target in GC treatment.

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Pharmacological Ascorbate Suppresses Growth of Gastric Cancer Cells with GLUT1 Overexpression and Enhances the Efficacy of Oxaliplatin Through Redox Modulation

Cited by 52 publications

References 47 publications

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome

Vitamin C Content in Fruits: Biosynthesis and Regulation

TRIM32 Promotes the Growth of Gastric Cancer Cells through Enhancing AKT Activity and Glucose Transportation

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