scholarly journals Insulin-Like Growth Factor-I Regulates Krüppel-Like Factor-6 Gene Expression in a p53-Dependent Manner

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1890-1897 ◽  
Author(s):  
Itay Bentov ◽  
Goutham Narla ◽  
Hagit Schayek ◽  
Kuhihara Akita ◽  
Stephen R. Plymate ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cancer Biology ◽  
Cell Cycle Progression ◽  
Human Colon ◽  
Dependent Manner ◽  
Human Colon Cancer ◽  
Western Blots ◽  
Increased Risk ◽  
Igf I

High-circulating IGF-I concentrations are associated with an increased risk for breast, prostate, and colorectal cancer. Krüppel-like factor-6 (KLF6) is a zinc finger tumor suppressor inactivated in prostate and other types of cancer. We have previously demonstrated that KLF6 is a potent transactivator of the IGF-I receptor promoter. The aim of the present study was to examine the potential regulation of KLF6 gene expression by IGF-I. The human colon cancer cell lines HCT116 +/+ and −/− (with normal and disrupted p53, respectively) were treated with IGF-I. Western blots, quantitative RT-PCR, and transfection assays were used to evaluate the effect of IGF-I on KLF-6 production. Signaling pathway inhibitors were used to identify the mechanisms responsible for regulation of KLF6 expression. Small interfering RNA against p53 and KLF6 was used to assess the role of p53 in regulation of KLF6 expression by IGF-I and to evaluate KLF6 involvement in cell cycle control. Results obtained showed that IGF-I stimulated KLF-6 transcription in cells with normal, but not disrupted, p53, suggesting that KLF6 is a downstream target for IGF-I action. Stimulation of KLF6 expression by IGF-I in a p53-dependent manner may constitute a novel mechanism of action of IGF-I, with implications in normal cell cycle progression and cancer biology.

scholarly journals Quantitative analysis of the level of p53 and p21(WAF1) mRNA in human colon cancer HT-29 cells treated with inositol hexaphosphate.

2006 ◽  
Vol 53 (2) ◽  
pp. 349-356 ◽  
Author(s):  
Ludmiła Weglarz ◽  
Izabela Molin ◽  
Arkadiusz Orchel ◽  
Beata Parfiniewicz ◽  
Zofia Dzierzewicz
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Progression ◽  
Mrna Level ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Cycle Progression ◽  
Inositol Hexaphosphate ◽  
P21 Waf1 ◽  
Ht 29

The aim of this study was to analyze the molecular mechanism of inositol hexaphosphate (InsP(6)) action through which it may inhibit proliferation of colon cancer cells and cell cycle progression. A kinetic study of p53 and p21(WAF1) mRNA increase was performed on human colon cancer HT-29 cells after treatment with 1, 5 and 10 mM InsP(6) for 6, 12, 24 and 48 h. Real-time-QPCR based on TaqMan methodology was applied to analyze quantitatively the transcript levels of these genes. The transcription of beta-actin and GAPDH genes was assessed in parallel to select the control gene with least variability. The 2(-Delta Delta Ct) method was used to analyze the relative changes in gene transcription. InsP(6) stimulated p53 and p21(WAF1) expression at the mRNA level, with the highest increase in p21(WAF1) mRNA occurring at 24 h, i.e., following the highest increase in p53 mRNA observed at 12 h. Based on these studies it may be concluded that the ability of InsP(6) to arrest the cell cycle may be mediated by the transcriptional up-regulation of the p53-responsive p21(WAF1) gene.

scholarly journals Imperatorin as a Promising Chemotherapeutic Agent against Human Larynx Cancer and Rhabdomyosarcoma Cells

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2046 ◽  
Author(s):  
Aneta Grabarska ◽  
Krystyna Skalicka-Woźniak ◽  
Michał Kiełbus ◽  
Magdalena Dmoszyńska-Graniczka ◽  
Paulina Miziak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Cancer Cell Lines ◽  
Larynx Cancer ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Angelica Archangelica

Naturally occurring coumarins are bioactive compounds widely used in Asian traditional medicine. They have been shown to inhibit proliferation, induce apoptosis, and/or enhance the cytotoxicity of currently used drugs against a variety of cancer cell types. The aim of our study was to examine the antiproliferative activity of different linear furanocoumarins on human rhabdomyosarcoma, lung, and larynx cancer cell lines, and dissolve their cellular mechanism of action. The coumarins were isolated from fruits of Angelica archangelica L. or Pastinaca sativa L., and separated using high-performance counter-current chromatography (HPCCC). The identity and purity of isolated compounds were confirmed by HPLC-DAD and NMR analyses. Cell viability and toxicity assessments were performed by means of methylthiazolyldiphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. Induction of apoptosis and cell cycle progression were measured using flow cytometry analysis. qPCR method was applied to detect changes in gene expression. Linear furanocoumarins in a dose-dependent manner inhibited proliferation of cancer cells with diverse activity regarding compounds and cancer cell type specificity. Imperatorin (IMP) exhibited the most potent growth inhibitory effects against human rhabdomyosarcoma and larynx cancer cell lines owing to inhibition of the cell cycle progression connected with specific changes in gene expression, including CDKN1A. As there are no specific chemotherapy treatments dedicated to laryngeal squamous cell carcinoma and rhabdomyosarcoma, and IMP seems to be non-toxic for normal cells, our results could open a new direction in the search for effective anti-cancer agents.

scholarly journals Ethanol, Zn2+ and insulin interact as progression factors to enhance DNA synthesis synergistically in the presence of Ca2+ and other cell cycle initiators in fibroblasts

2000 ◽  
Vol 346 (1) ◽  
pp. 241-247 ◽  
Author(s):  
Jin-Sheng HUANG ◽  
Qing-Bai SHE ◽  
Karan S. CRILLY ◽  
Zoltan KISS
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
Synergistic Effects ◽  
Dependent Manner ◽  
Cycle Progression ◽  
3T3 Fibroblasts ◽  
Igf I ◽  
Nih 3T3

In serum-starved NIH 3T3 fibroblasts, ethanol (30-80 mM) promoted the effects of insulin and insulin-like growth factor I (IGF-I) on DNA synthesis in a Zn2+-dependent manner. Ethanol and Zn2+ were most effective when added shortly before or after insulin, indicating that all these agents facilitated cell cycle progression. The synergistic effects of ethanol, Zn2+ and insulin (or IGF-I) on DNA synthesis required 1.1-2.3 mM Ca2+, which seemed to act as the cell cycle initiator. When serum-starved cells were pretreated for 2 h with other cell cycle initiators such as 10% (v/v) serum, 50 ng/ml platelet-derived growth factor or 2 ng/ml fibroblast growth factor, subsequent co-treatments with 60 mM ethanol, Zn2+ and insulin for an 18 h period again synergistically increased DNA synthesis. Of the various signal transducing events examined, ethanol stimulated cellular uptake of 45Ca and it enhanced the stimulatory effects of insulin on p70 S6 kinase activity in a Zn2+-dependent manner. In contrast, ethanol inhibited insulin-induced activating phosphorylation of p42/p44 mitogen-activated protein kinases; these inhibitory ethanol effects were prevented by Zn2+. The results show that, in NIH 3T3 fibroblasts, ethanol can promote cell cycle progression in the presence of a cell cycle initiator as well as Zn2+ and insulin (or IGF-I).

scholarly journals Design, Synthesis, Antitumor activity, cell cycle analysis and ELISA assay for Cyclin Dependant Kinase-2 of a new (4-aryl-6-flouro-4H-benzo[4, 5] thieno[3, 2-b] pyran) derivatives.

2017 ◽  
Vol 6 (5) ◽  
pp. 165-179 ◽  
Author(s):  
Ashraf Mouineer ◽  
Ashraf Zaher ◽  
Afaf El-Malah ◽  
Eman Abdel-Fattah Sobh
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Cell Cycle Progression ◽  
Human Colon ◽  
Time Interval ◽  
Human Colon Cancer ◽  
Cycle Progression ◽  
Design Synthesis ◽  
Affect Cell Cycle Progression ◽  
Ht 29

A series of benzo[b]thiophene and their benzo[4,5]thieno[3,2-b]pyran derivatives (3a-f), (4a-f), (5a-f) and 6 were synthesized and characterized by spectroscopic and elemental analysis. All compounds were subjected to one dose anticancer screening in NCI- America, but only the compounds gave high percent growth inhibition were further subjected to five dose screening. A good result of compound 4f with GI50 = 0.15 µmol, TGI= 1.14 µmol and 4c with GI50 = 1.09 µmol, TGI = 10.19 µmol, LC50 = 100 µmol on HT-29 cell line. To explore mechanism of cytotoxicity, compound 4f and 4c were allowed to affect cell cycle progression using HT-29 cell line (human colon cancer) in two-time interval (24 and 48 hr). The cytotoxicity of 4f and 4c was correlated with induction of apoptosis causing pre-G1apoptosis and cell growth arrest at G2/M in a time dependant manner through inhibition of CDK-2. For exploring the SAR for all synthesized compounds, IC50 of 5d was determined which was equal to 0.32 ±0.05 µmol, IC50 of 6 was equal to be 0.15 ±0.01 µmol while IC50 of erlotinib reference was equal to 0.3±0.02 µmol. Finally we were able to synthesize a series of benzo[b] thiophene, benzo[4,5]thieno[3,2-b]pyran having a good cytotoxic activity suggesting promising anticancer derivatives.

scholarly journals Radiation-Stimulated ERK1/2 and JNK1/2 Signaling can Promote Cell Cycle Progression in Human Colon Cancer Cells

Cell Cycle ◽  
2005 ◽  
Vol 4 (3) ◽  
pp. 456-464 ◽  
Author(s):  
Ruben W. Caron ◽  
Adly Yacoub ◽  
Clint Mitchell ◽  
Xiaoyu Zhu ◽  
Young Hong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Cycle Progression ◽  
Promote Cell Cycle Progression ◽  
Human Colon Cancer Cells
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