Diethyl maleate inhibits MCA+TPA transformed cell growth via modulation of GSH, MAPK, and cancer pathways

Priya, Shivam; Nigam, Akanksha; Bajpai, Preeti; Kumar, Sushil

doi:10.1016/j.cbi.2014.04.018

Cited by 8 publications

(4 citation statements)

References 48 publications

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“…It should be mentioned that in normal cells, this scenario would lead to disruption of cell redox homeostasis and to oxidant environment; however, this is not a rule in cancer, and in our Caco-2 cells we observed an increase of total thiols (protein-SH and GSH) after treatment with the compounds, co-existent with RONS generation. A high level of GSH is often observed in many human cancer cells, assumed to be a defense or an adaptive response against oxidative stress (Priya, Nigam, Bajpai, & Kumar, 2014), but in our case not enough to overcome the apoptotic fate caused by the treatment with phytochemicals. In addition, it should be mentioned that the total protein increased 1.5-2.5 folds in Caco-2 cells after all treatments (not shown), indicating a response in term of protein expression.…”

Section: Discussionmentioning

confidence: 99%

Anti-proliferative effect of main dietary phytosterols and β-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 – and oxidative stress-induced apoptosis

Cilla

Attanzio

Barberá

et al. 2015

Journal of Functional Foods

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Section: Discussionmentioning

confidence: 99%

Anti-proliferative effect of main dietary phytosterols and β-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 – and oxidative stress-induced apoptosis

Cilla

Attanzio

Barberá

et al. 2015

Journal of Functional Foods

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“…Here we applied these reporter cell lines to investigate the effect of two earlier mentioned, well-known inducers of the Nrf2 pathway, DEM and tBHQ, on the dynamics of Nrf2 and Srxn1 activation under different repeat exposure scenarios. DEM is an alkylating agent able to deplete cellular glutathione (GSH) levels by direct conjugation with GSH or via glutathione S-transferase (Casey et al 2002;Priya et al 2014;Yamauchi et al 2011). tBHQ is the metabolite of butylated hydroxyanisole, a synthetic phenolic antioxidant, that acts as a redox cycler to generate ROS (Imhoff and Hansen 2010).…”

Section: Introductionmentioning

confidence: 99%

A systematic analysis of Nrf2 pathway activation dynamics during repeated xenobiotic exposure

et al. 2018

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Oxidative stress leads to the activation of the Nuclear factor-erythroid-2-related factor 2 (Nrf2) pathway. While most studies have focused on the activation of the Nrf2 pathway after single chemical treatment, little is known about the dynamic regulation of the Nrf2 pathway in the context of repeated exposure scenarios. Here we employed single cell live imaging to quantitatively monitor the dynamics of the Nrf2 pathway during repeated exposure, making advantage of two HepG2 fluorescent protein reporter cell lines, expressing GFP tagged Nrf2 or sulfiredoxin 1 (Srxn1), a direct downstream target of Nrf2. High throughput live confocal imaging was used to measure the temporal dynamics of these two components of the Nrf2 pathway after repeated exposure to an extensive concentration range of diethyl maleate (DEM) and tert-butylhydroquinone (tBHQ). Single treatment with DEM or tBHQ induced Nrf2 and Srxn1 over time in a concentration-dependent manner. The Nrf2 response to a second treatment was lower than the response to the first exposure with the same concentration, indicating that the response is adaptive. Moreover, a limited fraction of individual cells committed themselves into the Nrf2 response during the second treatment. Despite the suppression of the Nrf2 pathway, the second treatment resulted in a three-fold higher Srxn1-GFP response compared to the first treatment, with all cells participating in the response. While after the first treatment Srxn1-GFP response was linearly related to Nrf2-GFP nuclear translocation, such a linear relationship was less clear for the second exposure. siRNA-mediated knockdown demonstrated that the second response is dependent on the activity of Nrf2. Several other, clinically relevant, compounds (i.e., sulphorophane, nitrofurantoin and CDDO-Me) also enhanced the induction of Srxn1-GFP upon two consecutive repeated exposure. Together the data indicate that adaptation towards prooxidants lowers the Nrf2 activation capacity, but simultaneously primes cells for the enhancement of an antioxidant response which depends on factors other than just Nrf2. These data provide further insight in the overall dynamics of stress pathway activation after repeated exposure and underscore the complexity of responses that may govern repeated dose toxicity.

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“…Figure 5C and 5D showed that the amounts of GSH and GSSG in CPB cells infected with ISKNV were increased. GSH ethyl ester (GSHe) is a GSH analog that can be transported across the cell membrane and is converted to free GSH [26, 27]. In the presence of lower concentrations of GSHe (0.1–1 mM) in the cell medium, the yield of ISKNV was enhanced in CPB cells (Figure 5E).…”

Section: Resultsmentioning

confidence: 99%

Glutamine and glutaminolysis are required for efficient replication of infectious spleen and kidney necrosis virus in Chinese perch brain cells

et al. 2016

Oncotarget

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Viruses rely on host cellular metabolism for energy and macromolecule synthesis during their replication. Infectious spleen and kidney necrosis virus (ISKNV) causes significant economic losses in the Chinese perch (Siniperca chuatsi) industry worldwide. However, little is known about the relationship between ISKNV replication and cellular metabolism. Using transcriptomic analysis, we observed that glutamine metabolism in Chinese perch brain (CPB) cells is altered during ISKNV infection. Moreover, ISKNV replication was decreased in CPB cells cultured in the glutamine-depleted medium. ISKNV replication was also inhibited in CPB cells cultured in the presence of bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (an inhibitor of glutaminase), (–)-epigallocatechinmo nogallate (an inhibitor of glutamate dehydrogenase) or L-buthionine sulfoximine (an inhibitor of glutathione synthesis). However, virus replication was rescued by the addition of multiple tricarboxylic acid cycle intermediates, ATP, or glutathione reduced ethyl ester. ATP and reduced glutathione/oxidized glutathione levels were increased in CPB cells infected with ISKNV, but were decreased in CPB cells cultured in glutamine-depleted medium. These results indicate ISKNV infection induces glutaminolysis to accommodate the biosynthetic and energy needs for its efficient virus replication.

show abstract

Diethyl maleate inhibits MCA+TPA transformed cell growth via modulation of GSH, MAPK, and cancer pathways

Cited by 8 publications

References 48 publications

Anti-proliferative effect of main dietary phytosterols and β-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 – and oxidative stress-induced apoptosis

Anti-proliferative effect of main dietary phytosterols and β-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 – and oxidative stress-induced apoptosis

A systematic analysis of Nrf2 pathway activation dynamics during repeated xenobiotic exposure

Glutamine and glutaminolysis are required for efficient replication of infectious spleen and kidney necrosis virus in Chinese perch brain cells

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