scholarly journals The Cyclin-dependent Kinase Inhibitors p15INK4Band p21CIP1Are Critical Regulators of Fibrillar Collagen-induced Tumor Cell Cycle Arrest

2007 ◽  
Vol 282 (33) ◽  
pp. 24471-24476 ◽  
Author(s):  
Steven J. Wall ◽  
Zhi-Duan Zhong ◽  
Yves A. DeClerck
Keyword(s):  
Cell Cycle ◽  
Tumor Cell ◽  
Cell Cycle Arrest ◽  
Kinase Inhibitors ◽  
Fibrillar Collagen ◽  
Cyclin Dependent Kinase ◽  
Cycle Arrest

Molecular response of human glioblastoma multiforme cells to ionizing radiation: cell cycle arrest, modulation of cyclin-dependent kinase inhibitors, and autophagy

2003 ◽  
Vol 98 (2) ◽  
pp. 378-384 ◽  
Author(s):  
Kevin C. Yao ◽  
Tadashi Komata ◽  
Yasuko Kondo ◽  
Takao Kanzawa ◽  
Seiji Kondo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Glioblastoma Multiforme ◽  
Ionizing Radiation ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Kinase Inhibitors ◽  
Cyclin Dependent Kinase ◽  
Content Type ◽  
Cycle Arrest ◽  
Fine Print

Object. Ionizing radiation is the gold-standard adjuvant treatment for glioblastoma multiforme (GBM), the most aggressive primary brain tumor. The mechanisms underlying neoplastic glial cell growth inhibition after administration of ionizing radiation, however, remain largely unknown. In this report, the authors characterize the response of GBM cells to ionizing radiation and elucidate factors that correlate with the radiosensitivity of these tumors. Methods. Six human GBM cell lines were subjected to increasing doses of radiation. Each demonstrated a dose-dependent suppression of cell proliferation. In the most radiosensitive cell line, the authors demonstrated a transient increase in the expression of the cyclin-dependent kinase inhibitors (CDKIs) p21 and p27, which corresponded with a G1 cell-cycle arrest. In contrast, the most radioresistant cell line demonstrated a decrease in p21 and p27 expression levels, which correlated with a failure to arrest. Apoptosis did not occur in any cell line following irradiation. Instead, autophagic cell changes were observed following administration of radiation, regardless of the relative radiosensitivity of the cell line. Conclusions. These findings elucidate some of the molecular responses of GBMs to irradiation and suggest novel targets for future therapy.

scholarly journals Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells

Oncogene ◽  
2003 ◽  
Vol 22 (51) ◽  
pp. 8271-8282 ◽  
Author(s):  
Chapla Agarwal ◽  
Rana P Singh ◽  
Sivanandhan Dhanalakshmi ◽  
Anil K Tyagi ◽  
Marianne Tecklenburg ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Colon Carcinoma ◽  
Kinase Inhibitors ◽  
Human Colon ◽  
Cyclin Dependent Kinase ◽  
Cycle Arrest ◽  
Human Colon Carcinoma ◽  
Ht 29

scholarly journals Discoidin Domain Receptor 2 Mediates Tumor Cell Cycle Arrest Induced by Fibrillar Collagen

2005 ◽  
Vol 280 (48) ◽  
pp. 40187-40194 ◽  
Author(s):  
Steven J. Wall ◽  
Erica Werner ◽  
Zena Werb ◽  
Yves A. DeClerck
Keyword(s):  
Cell Cycle ◽  
Tumor Cell ◽  
Cell Cycle Arrest ◽  
Fibrillar Collagen ◽  
Discoidin Domain Receptor ◽  
Cycle Arrest ◽  
Discoidin Domain Receptor 2

scholarly journals Novel Benzenesulfonate Scaffolds with a High Anticancer Activity and G2/M Cell Cycle Arrest

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1790
Author(s):  
Katarzyna Malarz ◽  
Jacek Mularski ◽  
Michał Kuczak ◽  
Anna Mrozek-Wilczkiewicz ◽  
Robert Musiol
Keyword(s):  
Cell Cycle ◽  
Anticancer Activity ◽  
Cell Cycle Arrest ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
P53 Protein ◽  
Structural Similarity ◽  
M Cell ◽  
Cycle Arrest ◽  
Small Series

Sulfonates, unlike their derivatives, sulphonamides, have rarely been investigated for their anticancer activity. Unlike the well-known sulphonamides, esters are mainly used as convenient intermediates in a synthesis. Here, we present the first in-depth investigation of quinazoline sulfonates. A small series of derivatives were synthesized and tested for their anticancer activity. Based on their structural similarity, these compounds resemble tyrosine kinase inhibitors and the p53 reactivator CP-31398. Their biological activity profile, however, was more related to sulphonamides because there was a strong cell cycle arrest in the G2/M phase. Further investigation revealed a multitargeted mechanism of the action that corresponded to the p53 protein status in the cell. Although the compounds expressed a high submicromolar activity against leukemia and colon cancers, pancreatic cancer and glioblastoma were also susceptible. Apoptosis and autophagy were confirmed as the cell death modes that corresponded with the inhibition of metabolic activity and the activation of the p53-dependent and p53-independent pathways. Namely, there was a strong activation of the p62 protein and GADD44. Other proteins such as cdc2 were also expressed at a higher level. Moreover, the classical caspase-dependent pathway in leukemia was observed at a lower concentration, which again confirmed a multitargeted mechanism. It can therefore be concluded that the sulfonates of quinazolines can be regarded as promising scaffolds for developing anticancer agents.

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