Mitochondrial glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase abrogate p53 induced apoptosis in a yeast model: Possible implications for apoptosis resistance in cancer cells

Redhu, Archana Kumari; Bhat, Jayadeva

doi:10.1016/j.bbagen.2019.129504

Cited by 8 publications

(7 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, CBD reduces oxidative stress, enhances mitochondrial function, and stimulates G6PDH activity and the pentose phosphate pathway (PPP) in cerebral ischemia ( Sun et al, 2017 ). However, enhancing PPP pathway components in mitochondria, such as G6PDH could, by reducing oxidative stress, suppress apoptosis and thus enhance oncogenesis ( Redhu and Bhat, 2020 ). This would begin to explain why a single compound can both be protective (e.g., in neurons) and capable of killing cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Modulates Mitochondrial Redox and Dynamics in MCF7 Cancer Cells: A Study Using Fluorescence Lifetime Imaging Microscopy of NAD(P)H

Mould

Botchway

Parkinson

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

The cannabinoid, cannabidiol (CBD), is part of the plant's natural defense system that when given to animals has many useful medicinal properties, including activity against cancer cells, modulation of the immune system, and efficacy in epilepsy. Although there is no consensus on its precise mode of action as it affects many cellular targets, CBD does appear to influence mitochondrial function. This would suggest that there is a cross-kingdom ability to modulate stress resistance systems that enhance homeostasis. As NAD(P)H autofluorescence can be used as both a metabolic sensor and mitochondrial imaging modality, we assessed the potential of this technique to study the in vitro effects of CBD using 2-photon excitation and fluorescence lifetime imaging microscopy (2P-FLIM) of NAD(P)H against more traditional markers of mitochondrial morphology and cellular stress in MCF7 breast cancer cells. 2P-FLIM analysis revealed that the addition of CBD induced a dose-dependent decrease in bound NAD(P)H, with 20 µM treatments significantly decreased the contribution of bound NAD(P)H by 14.6% relative to the control (p < 0.001). CBD also increased mitochondrial concentrations of reactive oxygen species (ROS) (160 ± 53 vs. 97.6 ± 4.8%, 20 µM CBD vs. control, respectively, p < 0.001) and Ca2+ (187 ± 78 vs. 105 ± 10%, 20 µM CBD vs. the control, respectively, p < 0.001); this was associated with a significantly decreased mitochondrial branch length and increased fission. These are all suggestive of mitochondrial stress. Our results support the use of NAD(P)H autofluorescence as an investigative tool and provide further evidence that CBD can modulate mitochondrial function and morphology in a dose-dependent manner, with clear evidence of it inducing oxidative stress at higher concentrations. This continues to support emerging data in the literature and may provide further insight into its overall mode of action, not only in cancer, but potentially its function in the plant and why it can act as a medicine.

show abstract

Section: Introductionmentioning

confidence: 99%

Cannabidiol Modulates Mitochondrial Redox and Dynamics in MCF7 Cancer Cells: A Study Using Fluorescence Lifetime Imaging Microscopy of NAD(P)H

Mould

Botchway

Parkinson

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…NADPH is an important substance in yeast in response to oxidative stress, which acts on glutathione to eliminate intracellular ROS in yeast 71 . NADPH is produced and utilized in the metabolism of pentose phosphate and TCA 55,72 . As shown in Table 12, the content of NADPH can reflect the antioxidant status of yeast and indirectly reflect the stress intensity of yeast under different glucose levels.…”

Section: Resultsmentioning

confidence: 99%

Effect of glucose levels on carbon flow rate, antioxidant status, and enzyme activity of yeast during fermentation

2022

View full text Add to dashboard Cite

BACKGROUND:The physiological metabolism of yeast has a significant impact on the quality of fermentation products. The present study aimed to investigate yeast metabolism in response to a changing glucose content environment, especially in fermentation products, as well as the change of carbon flow rate, antioxidant status, and yeast enzyme activity. RESULTS: Yeast in a 0 g L −1 glucose level was subjected to carbon starvation stress, cell growth retardation and cell proliferation was significantly inadequate; in the logarithmic growth stage of yeast, at a 30 g L −1 glucose level, the carbon source mainly flowed to tricarboxylic acid cycle and pentose phosphate metabolism, cell division, proliferation, and increased cell growth. In later logarithmic growth period and stable period, carbon flowed into glycerol and trehalose metabolism, to cope with the environmental stress; yeast in 60 and 150 g L −1 glucose levels faced high glucose stress at the beginning, the content of reactive oxygen increased, malondialdehyde content increased, cell damage was reduced through the regulation of superoxide dismutase and catalase enzyme activities, and most of the carbon flowed into the metabolic pathway of ethanol, glycerol, and trehalose to cope with high glucose stress, the pentose phosphate pathway showed a large late influx, and NADPH also started to increase rapidly after 24 h. CONCLUSION: Yeast was stressed in a high-sugar environment and ensured the activity of yeast by preferentially increasing the metabolic intensity of trehalose, glycerol, and glycolytic metabolism, weakening tricarboxylic acid metabolism, and first weakening and then increasing pentose phosphate metabolism.

show abstract

“…It is well established in the literature that HK, when bound to mitochondria, shows an increased ability to phosphorylate glucose since it is not inhibited by its product, G6P (38,61). In addition, there is a crosstalk between mitochondrial HKII and PPP, since the production of G6P serves as subsidy for G6PDH to trigger its functions in the cell (62,63). Redhu and Bhat also showed that, by interfering with the interaction between HK and mitochondria, G6PDH levels were reduced, raising mitochondrial ROS levels (63).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, there is a crosstalk between mitochondrial HKII and PPP, since the production of G6P serves as subsidy for G6PDH to trigger its functions in the cell (62,63). Redhu and Bhat also showed that, by interfering with the interaction between HK and mitochondria, G6PDH levels were reduced, raising mitochondrial ROS levels (63). Therefore, we propose that the removal of HK from the mitochondrial membrane would cause a decrease in the production of G6P, which, in turn, would not be available to enter the PPP on a large scale.…”

Section: Discussionmentioning

confidence: 99%

Detachment of Hexokinase II From Mitochondria Promotes Collateral Sensitivity in Multidrug Resistant Chronic Myeloid Leukemia Cells

et al. 2022

View full text Add to dashboard Cite

Chronic Myeloid Leukemia is a neoplastic disease characterized by the abnormal expansion of hematopoietic cells with compromised functions. Leukemic cells often display a multidrug resistance phenotype, enabling them to evade a number of structurally unrelated cytotoxic compounds. One of those mechanisms relies on the high expression of efflux transporters, such as the ABC proteins, whose activity depends on the hydrolysis of ATP to reduce intracellular drug accumulation. In the present work, we employed a well-known erythroleukemia cell line, K562, and a multidrug resistant derivative cell, FEPS, to evaluate how hexokinase II, a key regulator for the rate-limiting step glycolysis, contributes to the establishment of the multidrug resistance phenotype. We found that multidrug resistant cells primarily resort to glycolysis to generate ATP. Clotrimazole reduced the expression of mitochondrial hexokinase II, which destabilized bioenergetic parameters such as reactive oxygen species production, ATP, and glutathione levels on multidrug resistant cells. This impaired the activity of ABCC1, leading to increased drug accumulation and cell death. In summary, we propose that decoupling of hexokinase II from the mitochondria emerges as a promising strategy to generate collateral sensitivity and aid in the management of chronic myeloid leukemia in chemotherapy-refractory patients.

show abstract

Mitochondrial glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase abrogate p53 induced apoptosis in a yeast model: Possible implications for apoptosis resistance in cancer cells

Cited by 8 publications

References 42 publications

Cannabidiol Modulates Mitochondrial Redox and Dynamics in MCF7 Cancer Cells: A Study Using Fluorescence Lifetime Imaging Microscopy of NAD(P)H

Cannabidiol Modulates Mitochondrial Redox and Dynamics in MCF7 Cancer Cells: A Study Using Fluorescence Lifetime Imaging Microscopy of NAD(P)H

Effect of glucose levels on carbon flow rate, antioxidant status, and enzyme activity of yeast during fermentation

Detachment of Hexokinase II From Mitochondria Promotes Collateral Sensitivity in Multidrug Resistant Chronic Myeloid Leukemia Cells

Contact Info

Product

Resources

About