scholarly journals Differential Effects of Selective COX-2 Inhibitors on Cell Cycle Regulation and Proliferation of Glioblastoma Cell Lines

2004 ◽  
Vol 3 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Adel Kardosh ◽  
Martina Blumenthal ◽  
Wei Jun Wang ◽  
Thomas C. Chen ◽  
Axel H. Schonthal
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cell Cycle Regulation ◽  
Glioblastoma Cell ◽  
Differential Effects ◽  
Cox 2 ◽  
Cycle Regulation ◽  
Cox 2 Inhibitors ◽  
Glioblastoma Cell Lines

scholarly journals Absence of p53-dependent cell cycle regulation in pluripotent mouse cell lines

Oncogene ◽  
1998 ◽  
Vol 16 (23) ◽  
pp. 3003-3011 ◽  
Author(s):  
Prabha K Schmidt-Kastner ◽  
Karen Jardine ◽  
Michelle Cormier ◽  
Michael W McBurney
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cell Cycle Regulation ◽  
Mouse Cell ◽  
Dependent Cell ◽  
Cycle Regulation

Brefeldin A Induces Apoptosis and Cell Cycle Blockade in Glioblastoma Cell Lines

Oncology ◽  
2003 ◽  
Vol 64 (4) ◽  
pp. 459-467 ◽  
Author(s):  
Isabelle Pommepuy ◽  
Faraj Terro ◽  
Barbara Petit ◽  
Frank Trimoreau ◽  
Virginie Bellet ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Brefeldin A ◽  
Glioblastoma Cell ◽  
Glioblastoma Cell Lines

Activity of CDK1/2 Inhibitor LCQ195 Against Multiple Myeloma Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1519-1519 ◽  
Author(s):  
Douglas W. McMillin ◽  
Jake Delmore ◽  
Joseph M. Negri ◽  
Patrick Hayden ◽  
Nicholas Mitsiades ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Cell Cycle Regulation ◽  
Distinct Pattern ◽  
Marrow Stromal Cells ◽  
Drug Resistant ◽  
Ic50 Values ◽  
Cycle Regulation

Abstract Context: Conceptually, targeting proteins involved in cell cycle regulation is an appealing therapeutic strategy for multiple myeloma (MM), given the increased proliferative rate of biologically aggressive multi-drug resistant MM cells compared to not only their normal plasma cell counterparts, but also MM cells from earlier stages of the disease. Within the intricate network of signaling cascades and regulatory checkpoints involved in cell cycle progression and survival of neoplastic cells, cyclin-dependent kinases (CDKs) have emerged as intriguing therapeutic targets. We report the results of preclinical studies on the anti-MM activity of the selective CDK1/2 small molecule inhibitor NVP-LCQ195/AT9311 (Novartis Pharma/Astex Therapeutics). Methods/Results: In MTT colorimetric survival assays against a panel of 28 human MM cell lines, NVP-LCQ195 exhibited dose-dependent anti-MM activity, with IC50 values at or below ~0.5 μM (a pharmacologically relevant concentration) for 12 of 28 cell lines many of which are resistant to conventional or novel anti-MM therapies (e.g. dexamethasone, melphalan, thalidomide derivatives). NVP-LCQ195 was also active against primary MM cells isolated from heavily-pretreated/drug-resistant cases of MM. In marked contrast, the IC50 values of NVP-LCQ195 against non-malignant cells such as bone marrow stromal cells (BMSCs) and immortalized hepatocyte cells was >4 μM. In addition, both PHA-stimulated and unstimulated normal donor PBMCs were less sensitive than the majority of MM cell lines of our panel. Treatment with NVP-LCQ195 was able to overcome the protective effects conferred on MM cells by exogenous IL-6 (10ng/mL) or IGF-1 (50ng/mL), as well as by co-culture of MM cells with bone marrow stromal cells (BMSCs). NVP-LCQ195 was observed to trigger a distinct pattern of S-phase arrest, followed by eventual induction of apoptotic cell death. Mechanistic studies revealed that hsp90, B-raf, cyclin D1, and cyclin E2 levels decrease in response to NVP-LCQ195 treatment, while caspases- 3, -8 and PARP are cleaved within 16 and 24 hrs of drug treatment. We evaluated a series of combinations of this agent with conventional (e.g. dexamethasone, doxorubicin) and novel (e.g. bortezomib) anti-MM agents. No evidence of antagonism with any of these anti-MM agents was observed, indicating that combinations of NVP-LCQ195 with the aforementioned anti-MM agents can be feasible in clinical settings. Conclusion: Functional inhibition of proteins involved in cell cycle regulation remains an attractive approach for the treatment of MM. Treatment of MM cells with the CDK1/2 inhibitor NVP-LCQ195 induces, in a subset of MM cell lines, a distinct pattern of initial cell cycle arrest, anti-proliferative/pro-apoptotic molecular sequleae and eventual induction of cell death. Our results determine intriguing potential combination regimens for MM treatment. Further in vitro and in vivo studies are attempting to delineate molecular markers of MM cell responsiveness vs. resistance to NVP-LCQ195 and provide a framework for individualized treatment of select MM patients with this interesting class of compounds.

Effect of a combination of S-1 and gemcitabine on cell cycle regulation in pancreatic cancer cell lines

2012 ◽  
Vol 23 (5) ◽  
pp. 505-514 ◽  
Author(s):  
Yoshihito Morimoto ◽  
Osamu Takeuchi ◽  
Asako Takizawa ◽  
Hiroshi Yoneyama ◽  
Fumiki Asanuma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Cycle Regulation ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Cycle Regulation
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