Abstract
Focal adhesion is known to be highly expressed and activated in glioma cells. Recently, we demonstrated that FAK autophosphorylation inhibitor, Y15 significantly decreased tumor growth of DBTRG and U87 cells, especially in combination with temozolomide. In the present report, we performed gene expression analysis in these cells to reveal genes affected by Y15, temozolomide and combination of Y15 and temozolomide. We tested the effect of Y15 on gene expression by Illumina Human HT12v4 microarray assay and detected 8087 and 6555 genes, which were significantly either up- or down-regulated by Y15-treatment in DBTRG and U87 cells, respectively (p<0.05). Moreover, DBTRG and U87 cells treated with Y15 changed expression of 1332 and 462 genes more than 1.5 fold, p<0.05, respectively and had 237 common genes affected by Y15. The common genes up-regulated by Y15 included GADD45A, HSPA6 (heat-shock 70); DUSP1, DUSP 5 (dual-phosphatase 5); CDKN1A (p21) and common down-regulated genes included kinesins, such as KIF11, 14, 20A, 20B; topoisomerase II, TOP2A; cyclin F; cell cycle protein: BUB1; PARP1, POLA1. In addition, we detected genes affected by temozolomide and by combination of Y15 and temozolomide treatment in U87 cells. Among genes up-regulated by Y15 and temozolomide more significantly than by each agent alone were: COX7B; interferon, gamma-inducible transcript: IFI16; DDIT4; GADD45G and down-regulated: KIF3A, AKT1; ABL; JAK1, GLI3 and ALDH1A3. Thus, microarray gene expression analysis can be effective in establishing genes affected in response to FAK inhibitor alone and in response to combination of Y15 with temozolomide that is important for glioblastoma therapy.
Keywords: Autophosphorylation, brain, focal adhesion kinase, glioblastoma, inhibitor, Y397 site.
Anti-Cancer Agents in Medicinal Chemistry
Title:The Microarray Gene Profiling Analysis of Glioblastoma Cancer Cells Reveals Genes Affected by FAK Inhibitor Y15 and Combination of Y15 and Temozolomide
Volume: 14 Issue: 1
Author(s): Grace Huang, Baotran Ho, Jeffrey Conroy, Song Liu, Hu Qiang and Vita Golubovskaya
Affiliation:
Keywords: Autophosphorylation, brain, focal adhesion kinase, glioblastoma, inhibitor, Y397 site.
Abstract: Focal adhesion is known to be highly expressed and activated in glioma cells. Recently, we demonstrated that FAK autophosphorylation inhibitor, Y15 significantly decreased tumor growth of DBTRG and U87 cells, especially in combination with temozolomide. In the present report, we performed gene expression analysis in these cells to reveal genes affected by Y15, temozolomide and combination of Y15 and temozolomide. We tested the effect of Y15 on gene expression by Illumina Human HT12v4 microarray assay and detected 8087 and 6555 genes, which were significantly either up- or down-regulated by Y15-treatment in DBTRG and U87 cells, respectively (p<0.05). Moreover, DBTRG and U87 cells treated with Y15 changed expression of 1332 and 462 genes more than 1.5 fold, p<0.05, respectively and had 237 common genes affected by Y15. The common genes up-regulated by Y15 included GADD45A, HSPA6 (heat-shock 70); DUSP1, DUSP 5 (dual-phosphatase 5); CDKN1A (p21) and common down-regulated genes included kinesins, such as KIF11, 14, 20A, 20B; topoisomerase II, TOP2A; cyclin F; cell cycle protein: BUB1; PARP1, POLA1. In addition, we detected genes affected by temozolomide and by combination of Y15 and temozolomide treatment in U87 cells. Among genes up-regulated by Y15 and temozolomide more significantly than by each agent alone were: COX7B; interferon, gamma-inducible transcript: IFI16; DDIT4; GADD45G and down-regulated: KIF3A, AKT1; ABL; JAK1, GLI3 and ALDH1A3. Thus, microarray gene expression analysis can be effective in establishing genes affected in response to FAK inhibitor alone and in response to combination of Y15 with temozolomide that is important for glioblastoma therapy.
Export Options
About this article
Cite this article as:
Huang Grace, Ho Baotran, Conroy Jeffrey, Liu Song, Qiang Hu and Golubovskaya Vita, The Microarray Gene Profiling Analysis of Glioblastoma Cancer Cells Reveals Genes Affected by FAK Inhibitor Y15 and Combination of Y15 and Temozolomide, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (1) . https://dx.doi.org/10.2174/18715206113139990141
DOI https://dx.doi.org/10.2174/18715206113139990141 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Nanofibers: An Effective Tool for Controlled and Sustained Drug Delivery
Current Drug Delivery Synthesis, Cytotoxicity and Antimicrobial Activity of New Enmein-type Kauranoid Diterpenoid Derivatives
Anti-Cancer Agents in Medicinal Chemistry Curcumin Suppresses Tumor Growth and Angiogenesis in Human Glioma Cells Through Modulation of Vascular Endothelial Growth Factor/ Angiopoietin-2/Thrombospondin-1 Signaling
CNS & Neurological Disorders - Drug Targets Recent Patents in Circulating Cell-Free Tumor DNA as Biomarker in Cancer
Recent Patents on Biomarkers Strategies of overcoming the physiological barriers for tumor-targeted nano-sized drug delivery systems
Current Pharmaceutical Design Rho as a Target to Promote Repair: Translation to Clinical Studies with Cethrin
Current Pharmaceutical Design Recent Development of Peptide Drugs and Advance on Theory and Methodology of Peptide Inhibitor Design
Medicinal Chemistry Irreversible Inhibition of Serine Proteases – Design and In Vivo Activity of Diaryl α-Aminophosphonate Derivatives
Current Medicinal Chemistry Identifying Endogenous Neural Stem Cells in the Adult Brain In Vitro and In Vivo: Novel Approaches
Current Pharmaceutical Design Nanoparticles in Melanoma
Current Medicinal Chemistry Innovative Cancer Treatments that Augment Radiotherapy or Chemotherapy by the Use of Immunotherapy or Gene Therapy
Recent Patents on Anti-Cancer Drug Discovery Hitting the Golden TORget: Curcumin’s Effects on mTOR Signaling
Anti-Cancer Agents in Medicinal Chemistry Dysregulation of LncRNAs in Placenta and Pathogenesis of Preeclampsia
Current Drug Targets Targeting the Phosphatidylinositol 3-Kinase/AKT Pathway for the Treatment of Multiple Myeloma
Current Medicinal Chemistry Modulation of Immuno-biome during Radio-sensitization of Tumors by Glycolytic Inhibitors
Current Medicinal Chemistry The FDG-PET Revolution of Medical Imaging – Four Decades and Beyond
Current Molecular Imaging (Discontinued) STAT3 Regulation of Glioblastoma Pathogenesis
Current Molecular Medicine The Hydroxamic Acids as Potential Anticancer and Neuroprotective Agents
Current Medicinal Chemistry Curcumin and its Formulations: Potential Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Meet Our Co-Editor
Current Signal Transduction Therapy