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Anticancer activity and differentially expressed genes in head and neck cancer cells treated with a novel cyclin-dependent kinase inhibitor.

AbstractBACKGROUND:
Cyclin-dependent kinases (CDKs) are involved in the regulation of the cell cycle and the growth of tumor cells. In this study, we investigated the antitumor effect and differentially expressed genes (DEGs) in head and neck cancer cells treated by a novel CDK inhibitor, 2-[1,1'-biphenyl]- 4-yl-N-[5-(1,1-dioxo-1lambda(6)-isothiazolidin-2-yl)-1H-indazol-3-yl] acetamide (BAI).
METHODS:
Cell growth was measured by XTT assay. Cell cycle and apoptosis were determined using flow cytometry. GeneFishing PCR was utilized to identify DEGs. Protein expression was analyzed by Western blot.
RESULTS:
Exposure to BAI of 2 different head and neck cancer cell lines, AMC-HN4 and AMC-HN6, induced apoptosis in association with growth inhibition, cell cycle arrest, caspase-3 activation and cytochrome c release. Significantly, data from GeneFishing PCR experiments demonstrated 10 DEGs in AMC-HN6 cells treated with BAI. Some of these DEGs turned out to encode proteins with functions related to key cellular processes.
CONCLUSIONS:
These results indicate that BAI has strong anticancer activities on head and neck cancer cells, and the DEGs induced by BAI may become involved in BAI-induced cancer cell death.
AuthorsHo Cheol Shin, Dal Won Song, Won Ki Baek, Seong Ryong Lee, Taeg Kyu Kwon, Jinho Lee, Sol Hee Park, Byeong-Churl Jang, Jong-Wook Park
JournalChemotherapy (Chemotherapy) Vol. 55 Issue 5 Pg. 353-62 ( 2009) ISSN: 1421-9794 [Electronic] Switzerland
PMID19657189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2009 S. Karger AG, Basel.
Chemical References
  • 2-(1,1'-biphenyl)-4-yl-N-(5-(1,1-dioxo-1lambda(6)-isothiazolidin-2-yl)-1H-indazol-3-yl)acetamide
  • Antineoplastic Agents
  • Indazoles
  • Protein Kinase Inhibitors
  • Thiazolidines
  • Cytochromes c
  • Cyclin-Dependent Kinases
  • Type C Phospholipases
  • Caspase 3
Topics
  • Antineoplastic Agents (chemistry, pharmacology)
  • Apoptosis (drug effects)
  • Caspase 3 (metabolism)
  • Cell Line, Tumor
  • Cyclin-Dependent Kinases (antagonists & inhibitors)
  • Cytochromes c (metabolism)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Genes, Neoplasm (drug effects)
  • Head and Neck Neoplasms (drug therapy, genetics, metabolism)
  • Humans
  • Indazoles (pharmacology)
  • Protein Kinase Inhibitors (chemistry, pharmacology)
  • Thiazolidines (pharmacology)
  • Type C Phospholipases (metabolism)

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