The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

Riganti, Chiara; Gazzano, Elena; Polimeni, Manuela; Aldieri, Elisabetta; Ghigo, Dario

doi:10.1016/j.freeradbiomed.2012.05.006

Cited by 339 publications

(300 citation statements)

References 161 publications

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“…Enhanced glucose metabolism via glycolysis and the PPP also leads to the switch from the mitochondria-based and O 2 -dependent metabolism to a mainly anaerobic metabolism that can also reduce the levels of ROS generated by mitochondrial respiration chain. 31 In addition, c-myc has been demonstrated to enhance glutamine metabolism, which appears to be important for cell survival under oxygen-deprived conditions, 30,32 and we found that ASCT2 expression is Notch1-dependent in As 2 O 3 -transformed keratinocytes (Fig. 7).…”

Section: Discussionmentioning

confidence: 59%

“…29 It is well established that enhanced glycolysis is a distinctive and prominent feature of cancer cells (termed the Warburg effect) that promotes resistance to oxidative stress by diminishing mitochondrial oxidative phosphorylation and, in turn, ROS. 30,31 Interestingly, treatment with the glycolytic pathway inhibitor, 2-deoxy-D-glucose (2DG) (Fig. 4A and B), showed that As 2 O 3 -transformed HaCaT-R cells were more sensitive to 2-DG than the HaCat-sensitive cells.…”

Section: Notch1 Enhances Cell Survival In As 2 O 3 -Transformed Keratmentioning

confidence: 99%

“…Of note, arsenic trioxide-induced transformation of HaCaT cells resulted also in increased activity of the glucose-6-phosphate dehydrogenase (G6PD), the first enzyme of the pentose phosphate pathway (PPP). 31 The PPP supplies the cell with reducing equivalents such as NADPH, with ribose-5-phosphate, and with potential sources of ATP in the form of glycolytic intermediates. For these reasons, cells with active PPP are protected against oxidative stress and ROS-generating xenobiotics and have a proliferative advantage.…”

Section: Notch1 Enhances Cell Survival In As 2 O 3 -Transformed Keratmentioning

confidence: 99%

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Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

et al. 2014

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Section: Discussionmentioning

confidence: 59%

Section: Notch1 Enhances Cell Survival In As 2 O 3 -Transformed Keratmentioning

confidence: 99%

Section: Notch1 Enhances Cell Survival In As 2 O 3 -Transformed Keratmentioning

confidence: 99%

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Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

et al. 2014

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“…Although our data clearly suggest that SP did not protect lymphocytes against ROT-induced mitochondrial dysfunction and apoptosis, we do not discard the possibility that SP may serve as an H 2 O 2 scavenger under other specific experimental conditions (e.g., lymphocytes exposed to ROT in the presence of G plus SP). Our data thus suggest that G metabolism in non-dividing cells might be preferentially routed through the PPP (28,29) rather than the glycolysis pathway, which is the prevalent G metabolic route in active dividing cells when challenged with oxidant stressors (30,31). Interestingly, the inactivation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by H 2 O 2 may serve as a cellular switch to reroute the metabolic carbohydrate flux from glycolysis to the PPP under OS conditions (32).…”

Section: Discussionmentioning

confidence: 69%

“…These observations prompted us to evaluate the role of the PPP in this paradigm (28). PPP converts glucose to NADPH.…”

Section: Glucose Protects Lymphocytes Against Rotenone Through the Pementioning

confidence: 99%

Glucose promotes resistance in lymphocytes against oxidative stress-induced apoptosis through signaling and metabolic pathways. Implications for Parkinson’s disease

Bonilla-Rairez

Jiménez-Del-Río

Vélez-Pardo

2017

iatreia

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SUMMARYIntroduction: Parkinson's disease (PD) is a neurological disorder associated with the selective loss of dopaminergic (DAergic) neurons. Clinical data suggest that oxidative stress (OS) and dysregulation of glucose (G) metabolism are early events in PD. However, no data are available to explain the molecular connection between glucose metabolism, OS, and neuronal demise in PD. Human lymphocytes share a similar dopaminergic signaling mechanism with DAergic neurons. Further, rotenone (ROT) is a mitochondrial complex I inhibitor that selectively induces apoptosis through OS in dopaminergic neurons and lymphocytes. Thus, to test the hypothesis that G metabolism and OS are linked in dopaminergic system toxicity and PD, human lymphocytes were cultured with ROT in the presence or absence of various concentrations of glucose.

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High‐Z‐Sensitized Radiotherapy Synergizes with the Intervention of the Pentose Phosphate Pathway for In Situ Tumor Vaccination

et al. 2022

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Different from conventional vaccines, in situ vaccination could conveniently convert established tumors into a "vaccine factory" to release various tumor antigens for stimulating and diversifying antitumor T-cell response. [3] Radiation therapy (RT) is a widely used local therapy of malignancies and exhibits great potential in inducing in situ tumor vaccine effect. [4] However, even potentiated by CBI, RT could only lead to mild to moderate immune response within nonirradiated tumors, which is far less than medical needs. [5] Therefore, it is quite meaningful to boost RT-mediated in situ vaccination to extend its therapeutic effect to the whole body.To achieve this goal, a possible way could be potentiating RT-induced immunogenic cell death (ICD). ICD is a death modality accompanied by releasing tumor antigens and damage-associated molecular patterns, including calreticulin (CRT), high mobility group protein B1 (HMGB1), etc., which could provide antigens and adjuvants for tumor vaccination. [6] Currently, some studies have indicated that oxidative stress and DNA damage within tumor cells could potentially result in ICD. [7] However, due to the insufficient deposition of X-ray within tumor tissues, only low level of reactive oxygen species (ROS) could be produced to induce oxidative stress upon the recommended radiation doses. To address this problem, radiosensitizers based on high-Z elements are being developed widely to deposit X-ray for amplifying RT-induced oxidative stress. Of note, HfO 2 nanoparticles (Hensify) have been approved in Europe for locally advanced soft tissue sarcoma treatment [8] and are confirmed to augment RT-mediated antitumor immunity effect in many clinical trials. However, their slight improvements suggest the room for optimization. [9] The pentose phosphate pathway (PPP) is a branch of glycolysis and hyperactive in most tumors, [10] which could provide abundant NADPH and ribose 5-phosphate to maintain redox and nucleotides homeostasis, respectively. [11] NADPH is a central player in cellular antioxidant system, which not only mediates GSH synthesis, [12] but also acts as an electron donor to reduce oxidized GSH and thioredoxin (Trx, an important In situ tumor vaccination is preliminarily pursued to strengthen antitumor immune response. Immunogenic tumor cell death spontaneously releases abundant antigens and adjuvants for activation of dendritic cells, providing a paragon opportunity for establishing efficient in situ vaccination. Herein, Phy@PLGdH nanosheets are constructed by integrating physcion (Phy, an inhibitor of the pentose phosphate pathway (PPP)) with layered gadolinium hydroxide (PLGdH) nanosheets to boost radiation-therapy (RT)-induced immunogenic cell death (ICD) for potent in situ tumor vaccination. It is first observed that sheet-like PLGdH can present superior X-ray deposition and tumor penetrability, exhibiting improved radiosensitization in vitro and in vivo. Moreover, the destruction of cellular nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotide...

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The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

Cited by 339 publications

References 161 publications

Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

Glucose promotes resistance in lymphocytes against oxidative stress-induced apoptosis through signaling and metabolic pathways. Implications for Parkinson’s disease

High‐Z‐Sensitized Radiotherapy Synergizes with the Intervention of the Pentose Phosphate Pathway for In Situ Tumor Vaccination

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The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

Cited by 339 publications

References 161 publications

Loss of Notch1-dependent p21Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

Loss of Notch1-dependent p21Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

Glucose promotes resistance in lymphocytes against oxidative stress-induced apoptosis through signaling and metabolic pathways. Implications for Parkinson’s disease

High‐Z‐Sensitized Radiotherapy Synergizes with the Intervention of the Pentose Phosphate Pathway for In Situ Tumor Vaccination

Contact Info

Product

Resources

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Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis

Loss of Notch1-dependent p21^Waf1/Cip1expression influences the Notch1 outcome in tumorigenesis