The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

Bhatia, Maneet; Karlenius, Therese; Trapani, Jenny Di; Tonissen, Kathryn Fay

doi:10.5772/55185

Cited by 9 publications

(9 citation statements)

References 106 publications

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“…We verified the NOX2 expression immunohistochemically in the rat CBs of different groups which was earlier histochemically observed to be present in the type I cells and macrophages within the CB [28]. HIF2α is associated with adaptation to HA exposure [25] and mediates the increased expression of Sod2 gene encoding mitochondrial SOD2 [29,9]. SOD2 acts as an antioxidant which converts superoxide to hydrogen peroxide whose presence was also demonstrated immunohistochemically.…”

Section: Discussionsupporting

confidence: 68%

“…Previous workers have shown that HIF1α is found ubiquitously in vivo whereas HIF2α is tissue specific and is upregulated in specific cells of different organs [25,7]. However, both the isoforms of HIFα are expressed within the CB and are already considered as the master regulators of O 2 homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…The elevation of HIF1α that persists for a longer time, occurs during the re-oxygenation phase, lying between hypoxic episodes, where there is a generation of ROS that plays a vital role in this pattern of IH resembling OSA [10]. It has been reported in PC12 rat cells that HIF1α requires shorter hypoxic duration (4h) for its stabilization whereas HIF2α stabilization required longer hypoxic exposure (16h) [25]. The present study showed that exposure to the current pattern of IH resulted in no significant rise in the HIF1α levels but a highly significant rise in the HIF2α levels when compared with control.…”

Section: Discussionmentioning

confidence: 99%

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Alterations in Carotid Body Morphology and Cellular Mechanism Under the Influence of Intermittent Hypoxia

2017

IJCRR

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Aims: Intermittent hypoxia (IH) training is said to have a preconditioning effect for evoking acclimatization at high altitude (HA). Carotid body (CB) plays a vital role in oxygen sensing and is an important component in HA acclimatization. The present study reports the mechanistic effects of IH that involves episodes of hypoxia of few hours continued for several days, on the CB responses to acute hypobaric hypoxia in terms of morphological changes in CB and its cellular functions.Methodology: 24 Sprague-Dawley (250-300g) rats were divided into 2 major groups: 1) control, 2) experimental group (n=12 each) in which the rats were exposed to IH training for 10 days with a single hypoxic episode of 4h/day at a simulated altitude of 15000ft. 6 rats from each group were further subjected to a simulated hypobaric acute hypoxic (AH) challenge of 1hr at 25000ft to see the effect of IH training (IHT) and were named as 3) Control+ AH challenge and 4) IHT+ AH challenge. Morphological changes in CB in different groups were observed along with expression of hypoxia inducible factor (HIF) 1α, HIF2α, NADPH Oxidase 2 (NOX2) and Superoxide Dismutase 2 (SOD2) using immunohistochemistry for the first time. Results:The results showed that IH training leads to morphological changes in terms of hyperplasia and unaltered HIF1α levels along with a highly significant rise in HIF2α in CB. When the rats are exposed to AH without IH conditioning, there is a significant rise in HIF1α and thus NOX2 levels. However, prior exposure to IH leads to a significant rise in the HIF2α levels and thus SOD2 levels, when subjected to AH challenge. Discussion and Conclusion:These results indicate that IH training affects the cellular response of CB by regulating balanced expression of both HIF1α and HIF2α, thus modulating the cellular redox state by promoting the antioxidant enzyme production and suppressing the pro-oxidant enzyme levels, thereby playing a crucial role in pre-conditioning to acute hypoxia.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Alterations in Carotid Body Morphology and Cellular Mechanism Under the Influence of Intermittent Hypoxia

2017

IJCRR

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“…Several promoters directly or indirectly induce cell proliferation, recruit inflammatory cells, increase the production of reactive oxygen species (ROS) leading to oxidative damage to DNA and reduce DNA repair, resulting in replication of DNA and proliferation of cells that have lost normal growth control [6]. Studies have shown that ROS are activators of pro-angiogenic substances such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP), the goal of which is to induce angiogenesis [6,7].…”

Section: Introductionmentioning

confidence: 99%

Phytochemical screening, antioxidant, anti-inflammatory and antiangiogenic activities of Lophira procera A. Chev. (Ochnaceae) medicinal plant from Gabon

Misso

Sima-Obiang

Ndong

et al. 2018

Egyptian Journal of Basic and Applied Sciences

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The objective of this study was to perform phytochemical screening, to determine the content of phenolic compound, to evaluate antioxidant, anti-inflammatory and antiangiogenic activities of ethanol, waterethanol and water extracts of Lophira procera. Antioxidant activity was determined by 2,2-diphenyl-1picrylhydrazyl (DPPH) and phosphomolybdenum assay, anti-inflammatory activity by proteins denaturation inhibition and membranes stabilization test and antiangiogenic activity by chicken chorioallantoic membrane (CAM) method. The results showed that this plant is rich in saponins, polyphenols, tannins, total flavonoids, proanthocyanidins and coumarins. Extracts presented a strong antioxidant activity (IC 50 values of 5.452 ± 0.119 lg/mL and 6.346 ± 0.544 lg/mL and respective AAI of 9.173 ± 0.203 and 7. 919 ± 0.711). Excellent anti-inflammatory activity was also observed (IC 50 = 16.952 ± 1.897 and IC 50 = 2 3.172 ± 0.066 lg/mL for inhibition of protein denaturation and membrane stabilization respectively). Finally, extracts manifested a very good anti-angiogenic activity (with inhibitions ranging from 57.142 ± 0.124% to 100%). These biological activities are certainly due to high content of phenolic compound. This is the first study to report the phytochemical screening, the content of phenolic compound, the antioxidant, anti-inflammatory and antiangiogenic activities of extract derived from Lophira procera. The use of this plant in traditional medicine against ulcers, breast cancer, kidney and dental pain is therefore justified and its potential as a candidate for bioactive therapeutic molecule.

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“…The tumor microenvironment is characterized by hypoxia (a low partial pressure of oxygen: a low pO 2 ) and a highly reducing redox status [ 1 – 3 ]. Cancer cells are capable of surviving under hypoxic conditions by inducing the expression of metabolic enzymes required for anaerobic metabolism such as glycolysis.…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Tumor Redox Status in Head and Neck Cancer by 62Cu-ATSM PET

Tsujikawa

Asahi

et al. 2016

PLoS ONE

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PurposeTumor redox is an important factor for cancer progression, resistance to treatments, and a poor prognosis. The aim of the present study was to define tumor redox (over-reduction) using 62Cu-diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) PET and compare its prognostic potential in head and neck cancer (HNC) with that of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG).MethodsThirty HNC patients (stage II–IV) underwent pretreatment 62Cu-ATSM and 18F-FDG PET scans. Maximum standardized uptake values (SUVATSM and SUVFDG) and tumor-to-muscle activity concentration ratios (TMRATSM and TMRFDG) were measured. Reductive-tumor-volume (RTV) was then determined at four thresholds (40%, 50%, 60%, and 70% SUVATSM), and total-lesion-reduction (TLR) was calculated as the product of the mean SUV and RTV for 62Cu-ATSM. In 18F-FDG, metabolic-tumor-volume (MTV) and total-lesion-glycolysis (TLG) were obtained at a threshold of 40%. A ROC analysis was performed to determine % thresholds for RTV and TLR showing the best predictive performance, and these were then used to determine the optimal cut-off values to stratify patients for each parameter. Progression-free-survival (PFS) and cause-specific-survival (CSS) were evaluated by the Kaplan-Meier method.ResultsThe means ± standard deviations of PFS and CSS periods were 16.4±13.4 and 19.2±12.4 months, respectively. A ROC analysis determined that the 70% SUVATSM threshold for RTV and TLR was the best for predicting disease progression and cancer death. Optimal cut-offs for each index were SUVATSM = 3.6, SUVFDG = 7.9, TMRATSM = 3.2, TMRFDG = 5.6, RTV = 2.9, MTV = 8.1, TLR = 14.0, and TLG = 36.5. When the cut-offs for TMRATSM and TLR were set as described above in 62Cu-ATSM PET, patients with higher TMRATSM (p = 0.03) and greater TLR (p = 0.02) showed significantly worse PFS, while patients with greater TLR had significantly worse CSS (p = 0.02). Only MTV in 18F-FDG PET predicted differences in PSF and CSS (p = 0.03 and p = 0.03, respectively).ConclusionTumor redox parameters measured by 62Cu-ATSM PET may be determinants of HNC patient outcomes and help define optimal patient-specific treatments.

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The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

Cited by 9 publications

References 106 publications

Alterations in Carotid Body Morphology and Cellular Mechanism Under the Influence of Intermittent Hypoxia

Alterations in Carotid Body Morphology and Cellular Mechanism Under the Influence of Intermittent Hypoxia

Phytochemical screening, antioxidant, anti-inflammatory and antiangiogenic activities of Lophira procera A. Chev. (Ochnaceae) medicinal plant from Gabon

Assessment of the Tumor Redox Status in Head and Neck Cancer by 62Cu-ATSM PET

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