Docetaxel enhances apoptosis and G2/M cell cycle arrest by suppressing mitogen-activated protein kinase signaling in human renal clear cell carcinoma

Han, Tiandong; Shang, Donghao; Tian, Ye

doi:10.4238/gmr.15017321

Cited by 34 publications

(32 citation statements)

References 29 publications

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“…Docetaxel has been used to treat various types of cancers. In vitro, docetaxel suppresses proliferation and induces apoptosis by suppressing the mitogen-activated protein kinase (MAPK) signaling in renal cell carcinoma cells (28). Docetaxel induces cell apoptosis and suppresses cell proliferation in non-small cell lung cancer cells by upregulating microRNA-7 expression (29).…”

Section: Discussionmentioning

confidence: 99%

Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

Shao

Cui

et al. 2018

Oncol Rep

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Docetaxel is a front-line standard-of-care chemotherapeutic drug for the treatment of cancers. However, the underlying function and mechanism of docetaxel in human hepatocellular carcinoma (HCC) are uncertain. Therefore, the present study aimed to determine the effects of docetaxel on cell apoptosis and SOX2 expression in cultured human HCC stem cells. After human HCC stem cells were treated with docetaxel, cell proliferation was assessed by methyl thiazolyl tetrazolium (MTT) method, the cell apoptotic rate was evaluated by flow cytometry, the expression of CD133 and sex determining region Y-box 2 (SOX2) was determined by RT-PCR and immunohistochemistry, and the protein levels of CD133, SOX2, phosphoinositide 3-kinases (PI3K), AKT and phosphorylated AKT (p-AKT) were analyzed by western blotting. The results indicated that SOX2 and CD133 were highly expressed in patients with HCC while their expression was significantly decreased after patients with HCC were treated with docetaxel. In vitro, docetaxel inhibited the proliferation while it enhanced the apoptosis of human CD133-expressing HCC stem cells. Furthermore, lower expression of p-AKT and SOX2 were revealed in the presence of docetaxel. Notably, docetaxel-inhibited SOX2 expression and growth of human CD133-expressing HCC stem cells were partially restricted following the block of the PI3K/AKT signaling pathway using the inhibitor LY294002. The present study collectively indicated that docetaxel promoted apoptosis and upregulated SOX2 expression of human HCC stem cells through the suppression of the PI3K/AKT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

Shao

Cui

et al. 2018

Oncol Rep

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“…Cell line and animal data have identified upregulation of epigenetically silenced genes and consequent restoration of cell-cycle checkpoints as an important potential mechanism of action and indeed previous in vitro studies have correlated the antitumor activity of both AZA and DEC with their ability to effect changes in cell-cycle gene expression and induce G 2 phase arrest (7,23,24). Consequently, the observation that heterozygous predicted loss of function mutations in CDKN2A, a cell-cycle checkpoint activator, are correlated with decreased survival in AZA-treated patients is supportive of the hypothesis that induction of cell-cycle arrest is a potentially important mechanism of action of this agent.…”

Section: Discussionmentioning

confidence: 99%

Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular Signature

Craddock

Houlton

Quek

et al. 2017

Clinical Cancer Research

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Purpose: Azacitidine (AZA) is a novel therapeutic option in older patients with acute myeloid leukemia (AML), but its rational utilization is compromised by the fact that neither the determinants of clinical response nor its mechanism of action are defined. Co-administration of histone deacetylase inhibitors, such as vorinostat (VOR), is reported to improve the clinical activity of AZA, but this has not been prospectively studied in patients with AML.Experimental Design: We compared outcomes in 259 adults with AML (n ¼ 217) and MDS (n ¼ 42) randomized to receive either AZA monotherapy (75 mg/m 2 Â 7 days every 28 days) or AZA combined with VOR 300 mg twice a day on days 3 to 9 orally. Next-generation sequencing was performed in 250 patients on 41 genes commonly mutated in AML. Serial immunophenotyping of progenitor cells was performed in 47 patients.Results: Co-administration of VOR did not increase the overall response rate (P ¼ 0.84) or overall survival (OS; P ¼ 0.32). Specifically, no benefit was identified in either de novo or relapsed AML. Mutations in the genes CDKN2A (P ¼ 0.0001), IDH1 (P ¼ 0.004), and TP53 (P ¼ 0.003) were associated with reduced OS. Lymphoid multipotential progenitor populations were greatly expanded at diagnosis and although reduced in size in responding patients remained detectable throughout treatment.Conclusions: This study demonstrates no benefit of concurrent administration of VOR with AZA but identifies a mutational signature predictive of outcome after AZA-based therapy. The correlation between heterozygous loss of function CDKN2A mutations and decreased OS implicates induction of cell-cycle arrest as a mechanism by which AZA exerts its clinical activity.

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“…Also, stimulating alkaline phosphatase in renal tumor cell lines can deactivate ERK1/2; so, alkaline phosphatase may be used as a potential therapeutic target of RCC [117]. Docetaxel may suppress proliferation of RCC cells under in vitro and in vivo settings by suppressing cell growth, by inducing of both apoptosis and G2/M cell cycle arrest, which is related to reduced phosphorylation of ERK1/2 [118]. In vivo growth of a resistant to sunitinib human RCC cell line in nude mice is significantly inhibited after treatment with axitinib (compared to after treatment with sunitinib); accompanying the marked inhibition of angiogenesis, which proves that the antitumor activity of axitinib in RCC cells, at least in part, is involved in the inactivation of ERK1/2 [119].…”

Section: Erk1/2mentioning

confidence: 99%

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Luo

Shi

et al. 2016

Cell Physiol Biochem

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Tissue hypoxia/ischemia is a pathological feature of many human disorders including stroke, myocardial infarction, hypoxic/ischemic nephropathy, as well as cancer. In the kidney, the combination of limited oxygen supply to the tissues and high oxygen demand is considered the main reason for the susceptibility of the kidney to hypoxic/ischemic injury. In recent years, increasing evidence has indicated that a reduction in renal oxygen tension/blood supply plays an important role in acute kidney injury, chronic kidney disease, and renal tumorigenesis. However, the underlying signaling mechanisms, whereby hypoxia alters cellular behaviors, remain poorly understood. Mitogen-activated protein kinases (MAPKs) are key signal-transducing enzymes activated by a wide range of extracellular stimuli, including hypoxia/ischemia. There are four major family members of MAPKs: the extracellular signal-regulated kinases-1 and -2 (ERK1/2), the c-Jun N-terminal kinases (JNK), p38 MAPKs, and extracellular signal-regulated kinase-5 (ERK5/BMK1). Recent studies, including ours, suggest that these MAPKs are differentially involved in renal responses to hypoxic/ischemic stress. This review will discuss their changes in hypoxic/ischemic pathophysiology with acute kidney injury, chronic kidney diseases and renal carcinoma.

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Docetaxel enhances apoptosis and G2/M cell cycle arrest by suppressing mitogen-activated protein kinase signaling in human renal clear cell carcinoma

Cited by 34 publications

References 29 publications

Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular Signature

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

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