Search results for "p21"
showing 10 items of 131 documents
Lovastatin causes sensitization of HeLa cells to ionizing radiation‐induced apoptosis by the abrogation of G2 blockage
2003
To investigate the effect of inhibition of Ras/Rho-regulated signalling by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on radiation-induced cell killing and apoptosis.Different human cell lines were pretreated or not with lovastatin before exposure to gamma-rays. Afterwards, radiation-induced cell killing, formation and repair of double-strand breaks, activation of radiation-inducible signal mechanisms (i.e. p53, p21, extracellular-signal-related kinase (ERK), NF-kappaB), changes in cell cycle progression and apoptosis were analysed.As shown by a colony formation assay, lovastatin sensitized HeLa cells to gamma-radiation-induced cell killing. The lovastati…
Low doses of paclitaxel potently induce apoptosis in human retinoblastoma Y79 cells by up-regulating E2F1.
2008
Paclitaxel (PTX) is an anticancer drug currently in phase II clinical trials. This study shows for the first time that low doses of PTX (5 nM) potently induce apoptosis in human retinoblastoma Y79 cells. The effect of PTX is accompanied by a potent induction of E2F1 which appears to play a critical role in the effects induced by PTX. PTX induced a dose- and time-dependent effect, with G2/M arrest, cyclines A, E and B1 accumulation and a marked modification in the status of Cdc2-cyclin B1 complex, the major player of the G2/M checkpoint. Apoptosis followed G2/M arrest. An early and prolonged increase in p53 expression with its stabilization by phosphorylation and acetylation and its nuclear …
Loss of Neuroglobin Expression Alters Cdkn1a/Cdk6-Expression Resulting in Increased Proliferation of Neural Stem Cells
2018
Abstract: In the quest to unravel its functional significance, neuroglobin (Ngb), a brain-specific neuroprotective protein, has recently been proposed as an actor in neurodevelopment. As neural stem cells (NSCs) are fundamental during brain development, the present study aimed at investigating the role of Ngb in the growth and proliferation of NSCs by comparing an Ngb-floxed (Ngb(fl)-)NSC line, equivalent to the wild-type cellular situation, with an in-house created Ngb knockout (Ngb(KO)-)NSC line. Ngb(KO)-NSCs were characterized by an increased growth and proliferation capacity in vitro, supported by RNA sequencing and western blot results reporting the downregulation of Cdkn1a and the upr…
The structural plasticity of the C terminus of p21Cip1 is a determinant for target protein recognition.
2003
The cyclin-dependent kinase inhibitory protein p21(Cip1) might play multiple roles in cell-cycle regulation through interaction of its C-terminal domain with a defined set of cellular proteins such as proliferating cell nuclear antigen (PCNA), calmodulin (CaM), and the oncoprotein SET. p21(Cip1) could be described as an intrinsically unstructured protein in solution although the C-terminal domain adopts a well-defined extended conformation when bound to PCNA. However, the molecular mechanism of the interaction with CaM and the oncoprotein SET is not well understood, partly because of the lack of structural information. In this work, a peptide derived from the C-terminal domain of p21(Cip1) …
Multiple modes of cell death in neuroendocrine tumors induced by artesunate.
2020
Abstract Background The paucity of effective treatment in neuroendocrine tumors (NETs) encouraged us to investigate the therapeutic value of artesunate (ART) promised by its inhibitory effect against various tumors and broad safety profile. Methods We evaluated the impact of ART on three NET cell lines, BON-1, QGP-1 and NCI-H727 on cellular and molecular levels. Results Our results showed that ART induced endoplasmic reticulum (ER) stress through phosphorylation of eIF2α, which further gave rise to autophagy in all three NET cell lines. Specifically, apoptosis and ferroptosis were also observed in BON-1 cells, which made BON-1 cell line more vulnerable upon ART treatment. The different sens…
The role of p21Waf1/CIP1 as a Cip/Kip type cell-cycle regulator in oral squamous cell carcinoma (Review)
2013
Oral Squamous Cell Carcinoma (OSCC) is biologically characterized by the accumulation of multiple genetic and molecular alterations that end up clinically characterized as a malignant neoplasm through a phenomenon known as multistep. The members of the Cip/Kip family, specifically p21 Waf 1/CIP1 , are responsible for cell cycle control, blocking the transition from phase G1 to phase S. We made a search of articles of peer-reviewed Journals in PubMed/ Medline, crossing the keywords. The goal of this paper is to determine the relationship between p21 Waf 1/ CIP1 expression and several clinical and pathological aspects of OSCC, their relationship with p53 and HPV, as well as genetic alteration…
Prognostic Significance of Histopathological Grading and Immunoreactivity for p53 and p21/WAF1 in Grade 2 pTa Transitional Cell Carcinoma of …
2001
At present, there are no predictors of tumour behaviour for grade (G) 2 pTa transitional cell carcinomas (TCC) of the bladder. Here we analyse the prognostic relevance of histopathological grading and the immunohistochemical detection of p53 and p21/WAF1.70 patients were newly diagnosed with G2 pTa TCC of the bladder based on transurethral resection specimens. Two pathologists, blinded with respect to the clinical outcome, confirmed the initial grade and subclassified the G2 lesions into G2a and G2b carcinomas based on the degree of nuclear atypia and the number of mitoses. Immunoreactivity for p53 and p21/WAF1 was evaluated semiquantitatively.There were 52 G2a and 18 G2b tumours, mean foll…
Activated kRas protects colon cancer cells from cucurbitacin-induced apoptosis: The role of p53 and p21
2008
Cucurbitacins have been shown to inhibit proliferation in a variety of cancer cell lines. The aim of this study was to determine their biological activity in colon cancer cell lines that do not harbor activated STAT3, the key target of cucurbitacin. In order to establish the role of activated kRas in the responsiveness of cells to cucurbitacins, we performed experiments in isogenic colon cancer cell lines, HCT116 and Hke-3, which differ only by the presence of an activated kRas allele. We compared the activity of 23, 24-dihydrocucurbitacin B (DHCB) and cucurbitacin R (CCR), two cucurbitacins that we recently isolated, with cucurbitacin I (CCI), a cucurbitacin with established antitumorigeni…
Benzo[a]pyrene represses DNA repair through altered E2F1/E2F4 function marking an early event in DNA damage-induced cellular senescence
2020
AbstractTranscriptional regulation of DNA repair is of outmost importance for the restoration of DNA integrity upon genotoxic stress. Here we report that the potent environmental carcinogen benzo[a]pyrene (B[a]P) activates a cellular DNA damage response resulting in transcriptional repression of mismatch repair (MMR) genes (MSH2, MSH6, EXO1) and of RAD51, the central homologous recombination repair (HR) component, ultimately leading to downregulation of MMR and HR. B[a]P-induced gene repression is caused by abrogated E2F1 signalling. This occurs through proteasomal degradation of E2F1 in G2-arrested cells and downregulation of E2F1 mRNA expression in G1-arrested cells. Repression of E2F1-me…
The role of reactive oxygen species and subsequent DNA-damage response in the emergence of resistance towards resveratrol in colon cancer models
2014
AbstractIn spite of the novel strategies to treat colon cancer, mortality rates associated with this disease remain consistently high. Tumour recurrence has been linked to the induction of resistance towards chemotherapy that involves cellular events that enable cancer cells to escape cell death. Treatment of colon cancer mainly implicates direct or indirect DNA-damaging agents and increased repair or tolerances towards subsequent lesions contribute to generate resistant populations. Resveratrol (RSV), a potent chemosensitising polyphenol, might share common properties with chemotherapeutic drugs through its indirect DNA-damaging effects reported in vitro. In this study, we investigated how…