• 1998). p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells. (nature.com)
  • This gene encodes the cyclin-dependent kinase inhibitor p21(WAF1/Cip1), a factor implicated in cell cycle, senescence, and cancer. (ed.ac.uk)
  • This new and unprecedented evidence for a link between SdhD dysfunction and p21(WAF1/Cip1) will open new avenues for the study of the mechanisms that cause tumors in Sdh mutants. (ed.ac.uk)
  • The cyclin-dependent kinase inhibitor, p21 cip1/waf1 (p21), maintains hematopoietic stem cell quiescence, and we evaluated its role in the regenerative response of neural tissue after ischemic injury using the mice deficient in p21. (rupress.org)
  • Unlike iPS cells, undifferentiated FReP cells proliferate slowly and express low proto-oncogene c-MYC and unexpectedly high levels of cyclin-dependent kinase inhibitors p15(Ink4B) and p21(WAF1/Cip1). (ca.gov)
  • Remarkably, in a fashion reminiscent of quiescent stem cells, the slow replicative phenotype of undifferentiated FReP cells reverses after differentiation induction, with differentiating FReP cells proliferating faster and expressing less p15(Ink4B) and p21(WAF1/Cip1) than differentiating iPS cells. (ca.gov)
  • Purpose: The study investigated whether basal, constitutive levels of p21(WAF1/CIP1) protein in murine carcinoma are related to in vivo tumor radioresponse. (elsevierpure.com)
  • The study is based on recent observations demonstrating that in vitro cancer cell lines are resistant to cytotoxic drugs when they express high basal levels of p21(WAF1/CIP1) protein, and that the loss of the p21 gene in the HCT116 human colorectal cancer cell line results in increased radioresponse of xenografts derived from that cell line. (elsevierpure.com)
  • Methods and Materials: Protein levels of p21(WAF1/CIP1), p53, bax, and bcl-2 were determined in 8 carcinomas (3 mammary carcinomas designated MCa-4, MCa-29, and MCa-35, 2 squamous cell carcinomas designated SCC-IV and SCC-VII, ovarian adenocarcinoma OCa-I, hepatocarcinoma HCa-I, and adenosquamous carcinoma ACa SG) syngeneic to C3Hf/Kam mice using Western blot analysis. (elsevierpure.com)
  • Results: Protein levels of these oncogenes varied among tumors, with p21(WAF1/CIP1) showing the greates variation: its mean densitometric value ranged from 1 to 19. (elsevierpure.com)
  • Tumor radioresponse correlated significantly (R = 0.77, p = 0.02) only with the magnitude of p21(WAF1/CIP1) expression: tumors with high levels of p21(WAF1/CIP1) were less radiocurable than those with lower levels. (elsevierpure.com)
  • Despite a strong trend to correlation, (p = 0.15), p21(WAF1/CIP1) expression did not correlate significantly with radiation-induced apoptosis, which suggested that p21(WAF1/CIP1) influenced tumor radioresponse by mechanisms beyond that of apoptosis induction. (elsevierpure.com)
  • Conclusion: Our findings showed that murine tumors exhibit wide variation in constitutive levels of p21(WAF1/CIP1) which had a significant relationship with tumor radioresponse: tumors with high levels of p21(WAF1/CIP1) were less radiocurable than those with lower levels. (elsevierpure.com)
  • These findings support the concept that p21(WAF1/CIP1) is a major determinant of tumor radioresponse in vivo, and may have important clinical implications. (elsevierpure.com)
  • The pretreatment assessment of p21(WAF1/CIP1) protein could serve as a useful predictor of radiotherapy outcome and may assist in selecting an effective treatment modality. (elsevierpure.com)
  • Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
  • SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)
  • Primary mouse embryo fibroblasts lacking Cip1 and Kip1 genes encoding inhibitors of cyclin-dependent kinase-2 were used to further explore the effects of oncogenic Ras on arrest of the cell division cycle. (ku.dk)
  • Although early passage primary fibroblast strains that lack both p21(Cip1) and p27(Kip1) fail to assemble cyclin D-dependent kinases, oncogenic Ras retained its ability to induce p19(ARF), but not p16(INK4a), protecting Cip/Kip-null cells from proliferating and undergoing transformation. (ku.dk)
  • Therefore, in the absence of p16(INK4a), p21(Cip1), and p27(Kip1), oncogenic Ras affects the functions of genes required for completion of the cell cycle. (ku.dk)
  • Molecular mechanism of cell cycle blockage of hepatoma SK-Hep-1 cells by Epimedin C through suppression of mitogen-activated protein kinase activation and increased expression of CDK inhibitors p21(Cip1) and p27(Kip1). (jcimjournal.com)
  • ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. (biomedcentral.com)
  • Although carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes appear to be limited, INK4A is among the most commonly mutated genes in human tumors. (medscape.com)
  • The CDKN2A/B locus contains genes encoding cell cycle inhibitors, including p16 Ink4a , which have not yet been implicated in the control of hepatic glucose homeostasis. (diabetesjournals.org)
  • Additionally, the mRNA and protein expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (pRb), was further down-regulated under exposure to lovastatin in condition of BRCA1 overexpression, but the expression of p21WAF1/CIP1, a cyclin-dependent kinase inhibitor (CDKI), was further up-regulated, both in vitro and in vivo detected with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. (nih.gov)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • Although histone deacetylase (HDAC) inhibitors are known to suppress synovial sarcoma in vitro and in vivo , the exact mechanism is not clear. (nature.com)
  • In this study, we report a central role of the transcription factor, early growth response-1 (EGR1), in the regulation of HDAC inhibitor-induced apoptotic cell death in synovial sarcoma. (nature.com)
  • The SS18-SSX oncoprotein, characteristic of synovial sarcoma, maintains EGR1 expression at low levels, whereas it is significantly increased after HDAC inhibitor treatment. (nature.com)
  • On the contrary, EGR1 knockdown leads to a decrease in HDAC inhibitor-induced apoptosis. (nature.com)
  • Using a combination of gain- and loss-of-function approaches, we show that EGR1 modulation of PTEN contributes to HDAC inhibitor-induced apoptosis in synovial sarcoma. (nature.com)
  • Taken together, our findings indicate that SS18-SSX-mediated attenuation of an EGR1-PTEN network regulates synovial sarcoma cell survival, and that HDAC inhibitor-mediated apoptosis operates at least in part through reactivation of this pathway. (nature.com)
  • Inhibitors of histone deacetylase (HDAC) restore the p53 pathway in neuroblastoma cells. (nature.com)
  • Recently, VPA has demonstrated antitumor activity as a histone deacetylase (HDAC) inhibitor. (iiarjournals.org)
  • Since the recruitment of HDAC leads to transcriptional repression, inhibitors of this enzymatic activity can reverse aberrant repression in cancer cells and lead to re-expression of epigenetically silenced genes involved in growth and differentiation processes. (iiarjournals.org)
  • Therefore, HDAC inhibitors are considered as candidate drugs in cancer therapy ( 4 - 6 ). (iiarjournals.org)
  • We demonstrated previously that valproic acid (VPA) and other short-chain fatty acids, as HDAC inhibitors, can arrest cell growth and induce differentiation in human neuroblastoma cells ( 10 ). (iiarjournals.org)
  • The effectiveness of HDAC inhibitors, expecially VPA, in neuroblastoma cells, prompted us to investigate the anticancer activity of VPA in other neural crest-derived malignancies, such as glioblastoma, melanoma and Askin tumor. (iiarjournals.org)
  • 2006). Anticancer activities of histone deacetylase inhibitors. (nature.com)
  • CWR22Rv1 cells, a castrate-resistant prostate cancer cell line, were treated with Zyflamend and the expression of class I and II histone deacetylases, along with their downstream target the tumor suppressor gene p21, was investigated. (biomedcentral.com)
  • Expression of the tumor suppressor gene p21, a known downstream target of histone deacetylases and CBP/p300, was increased by Zyflamend treatment and the effect on p21 was, in part, mediated through Erk1/2. (biomedcentral.com)
  • Our results suggest that the extracts of this polyherbal combination increase histone 3 acetylation, inhibit the expression of class I and class II histone deacetylases, increase the activation of CBP/p300 and inhibit cell proliferation, in part, by up regulating p21 expression. (biomedcentral.com)
  • We have shown that colorectal cancer cell lines defective in DNA MMR exhibit an increased sensitivity to both camptothecin, a topoisomerase I inhibitor, and etoposide, a topoisomerase II inhibitor. (aacrjournals.org)
  • Involvement of p21 was confirmed with siRNA knockdown and over expression experiments. (biomedcentral.com)
  • Knockdown of p21 with siRNA technology attenuated Zyflamend-induced growth inhibition. (biomedcentral.com)
  • Our results suggest that BRCA1 overexpression sensitizes cancer cells to lovastatin via regulation of cyclin D1-CDK4-p21WAF1/CIP1 pathway, which will provide an innovative experimental framework to study control of breast cancer cell proliferation. (nih.gov)
  • Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • Because MMR is assumed to modulate cytotoxicity to various chemotherapeutic agents that act upon DNA, our objectives have been to define its possible involvement in the cytotoxicity of topoisomerase inhibitors. (aacrjournals.org)
  • Although steady-state conditions revealed no increase in primitive cell proliferation in p21-null mice, a significantly larger fraction of quiescent neural precursors was activated in the hippocampus and subventricular zone after brain ischemia. (rupress.org)
  • Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). (oncotarget.com)
  • We assessed whether cell cycle inhibitors that restrict stem cell populations in other tissues may participate in limiting neural stem cell reactivity in vivo. (rupress.org)
  • Over expression of p21 inhibited cell growth and concomitant treatment with Zyflamend enhanced this effect. (biomedcentral.com)
  • Oncogenic Ras induces p19ARF and growth arrest in mouse embryo fibroblasts lacking p21Cip1 and p27Kip1 without activating cyclin D-dependent kinases. (ku.dk)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
  • Our results also indicate that neither p53 status, nor cell cycle alterations correlate with the sensitivity of colorectal cancer cells to topoisomerase inhibitors. (aacrjournals.org)
  • Since the invasion process involves a complex system of tightly regulated proteases, matrix metalloproteinases (MMPs) and their tissue-specific inhibitors (TIMPs), the effect of VPA on MMP and TIMP expressions was analysed. (iiarjournals.org)
  • The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (cancerindex.org)