Cyclin-dependent kinase 2 inhibitor SU9516 increases sensitivity of colorectal carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737

Stefanikova, A.; Klacanova, Katarina; Pilchová, Ivana; Hatok, Jozef; Račay, Peter

doi:10.4149/gpb_2017030

Cited by 9 publications

(3 citation statements)

References 51 publications

(62 reference statements)

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“…In the case of well-established Caco-2 cells it is known that they express a large number of enzymes and transporter proteins present in normal human intestinal epithelium, but it is also known that the gene expression profiles of transformed epithelial cell lines like Caco-2, HT29 and normal human intestinal epithelium differ from each other. However, the differences are not only found between the cell lines and normal epithelium, but also between different cells lines, such as Caco-2 and HT29 cell lines [ 44 , 45 , 46 , 47 ]. Normal intestinal epithelium is made up of several different cell types, and differences in gene expression profiles are not only observed in the mucosal epithelium along the whole gastrointestinal tract, but also along the crypt-villus axis [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Oxygen Consumption Rate Analysis of Mitochondrial Dysfunction Caused by Bacillus cereus Cereulide in Caco-2 and HepG2 Cells

Decleer

Jovanović

Vakula

et al. 2018

Toxins

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The emetic syndrome of Bacillus cereus is a food intoxication caused by cereulide (CER) and manifested by emesis, nausea and in most severe cases with liver failure. While acute effects have been studied in the aftermath of food intoxication, an exposure to low doses of cereulide might cause unnoticed damages to the intestines and liver. The toxicity which relies on the mitochondrial dysfunction was assessed on Caco-2 and HepG2 cells after exposure of one, three and ten days to a range of low doses of cereulide. Oxygen consumption rate analyses were used to study the impact of low doses of CER on the bioenergetics functions of undifferentiated Caco-2 and HepG2 cells using Seahorse XF extracellular flux analyzer. Both Caco-2 and HepG2 cells experienced measurable mitochondrial impairment after prolonged exposure of 10 days to 0.25 nM of cereulide. Observed mitochondrial dysfunction was greatly reflected in reduction of maximal cell respiration. At 0.50 nM CER, mitochondrial respiration was almost completely shut down, especially in HepG2 cells. These results corresponded with a severe reduction in the amount of cells and an altered morphology, observed by microscopic examination of the cells. Accurate and robust quantification of basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity, and non-mitochondrial respiration allowed better understanding of the effects of cereulide in underlying respiratory malfunctions in low-dose exposure.

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Section: Resultsmentioning

confidence: 99%

Oxygen Consumption Rate Analysis of Mitochondrial Dysfunction Caused by Bacillus cereus Cereulide in Caco-2 and HepG2 Cells

Decleer

Jovanović

Vakula

et al. 2018

Toxins

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“…A synergistic effect of concurrent inhibition of bromodomain-containing protein 4 (BRD4) and CDK2 in MYC-amplified medulloblastoma was observed . Enhanced sensitivity of apoptotic-resistant cells was shown by combined inhibition of CDK2 and BCL-2 family proteins. , Besides a synergistic role, CDK2 inhibition also attenuates the development of resistance. Pharmacological or molecular targeting of CDK2 sensitizes BRAF and HSP90 inhibition-resistant melanoma cell lines .…”

Section: Rationale For Targeting Cdk2mentioning

confidence: 97%

Cyclin-Dependent Kinase 2 Inhibitors in Cancer Therapy: An Update

et al. 2018

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Cyclin-dependent kinase 2 (CDK2) drives the progression of cells into the S- and M-phases of the cell cycle. CDK2 activity is largely dispensable for normal development, but it is critically associated with tumor growth in multiple cancer types. Although the role of CDK2 in tumorigenesis has been controversial, emerging evidence proposes that selective CDK2 inhibition may provide a therapeutic benefit against certain tumors, and it continues to appeal as a strategy to exploit in anticancer drug development. Several small-molecule CDK2 inhibitors have progressed to the clinical trials. However, a CDK2-selective inhibitor is yet to be discovered. Here, we discuss the latest understandings of the role of CDK2 in normal and cancer cells, review the core pharmacophores used to target CDK2, and outline strategies for the rational design of CDK2 inhibitors. We attempt to provide an outlook on how CDK2-selective inhibitors may open new avenues for cancer therapy.

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“…Caco-2 cells are one of cancer cell lines that are deficient in p53 protein expression [15, 16]. However, Tsai et al [17] have reported that, independent of p53, activation of extracellular signal-regulated kinase (ERK) leads to both cell cycle arrest and apoptotic cell death via upregulation of p21 and downregulation of Bcl-2, respectively.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide donor GYY4137 suppresses proliferation of human colorectal cancer Caco-2 cells by inducing both cell cycle arrest and cell death

Sakuma

Minamino

Takase

et al. 2019

Heliyon

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Conflicting data regarding the ability of hydrogen sulfide (H 2 S), which reaches high levels in the large intestine owing to biosynthesis in the intestinal cells and intestinal bacteria, to promote or inhibit colorectal cancer cell proliferation have been reported recently. In the present study, the effect of H 2 S on the proliferation of the human colorectal cancer cell line Caco-2 was examined by using the H 2 S donor GYY4137. At concentrations of 0.5 mM and 1.0 mM, GYY4137 significantly inhibited Caco-2 cell viability. Cell cycle analysis, and apoptosis and necrosis detection revealed that the anti-proliferative effect of GYY4137 was partially attributable to the induction of S-G 2 /M cell cycle arrest, apoptosis and necrosis. These results suggest that H 2 S has the potential to suppress human colorectal cancer cell proliferation by influencing both cell cycle and cell death.

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Cyclin-dependent kinase 2 inhibitor SU9516 increases sensitivity of colorectal carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737

Cited by 9 publications

References 51 publications

Oxygen Consumption Rate Analysis of Mitochondrial Dysfunction Caused by Bacillus cereus Cereulide in Caco-2 and HepG2 Cells

Oxygen Consumption Rate Analysis of Mitochondrial Dysfunction Caused by Bacillus cereus Cereulide in Caco-2 and HepG2 Cells

Cyclin-Dependent Kinase 2 Inhibitors in Cancer Therapy: An Update

Hydrogen sulfide donor GYY4137 suppresses proliferation of human colorectal cancer Caco-2 cells by inducing both cell cycle arrest and cell death

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