title: Curbing the focal adhesion kinase and its associated signaling events by pentoxifylline in MDA-MB-231 human breast cancer cells.
abstract: Pentoxifylline (PTX) is a methylxanthine derivative currently being used in the treatment of peripheral vascular diseases. Recently, we had evaluated its action in human MDA-MB-231 breast cancer cells. PTX exhibited anti-metastatic activity by affecting key processes such as proliferation, adhesion, migration, invasion and apoptosis. In light of the preliminary findings, the present work accounts for the possible mechanistic insights of the pathways affected by PTX. Aberrant Focal Adhesion Kinase (FAK) signaling forms a key determinant in breast cancer and in view of this fact we had investigated downstream processes regulated by FAK. PTX at sub-toxic doses lowers the level of activated FAK, Extracellular Regulated Kinase or Mitogen Activated Protein Kinase (ERK/MAPK), Protein Kinase B (PKB/Akt) affecting cellular proliferation and survival. It blocks G1/S phase of cell cycle by inhibiting the expression of Cyclin D1/Cdk6. Further, it modulates the activities of RhoGTPases and alters actin organization resulting in decreased motility. PTX also delays tumor growth and inhibited blood vessel formation in vivo. In purview of these findings, PTX surely qualifies as a suitable prospect in the intervention of breast cancer.
authors.affiliation: Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India. peeyushgoel29@gmail.com
authors.forename: Peeyush N
authors.initials: PN
authors.lastname: Goel
authors.forename: Rajiv P
authors.initials: RP
authors.lastname: Gude
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D010431:Pentoxifylline / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D053148:Caspase 3; D053453:Caspase 9; D020741:rho GTP-Binding Proteins; D010431:Pentoxifylline
keywords: Apoptosis; Focal Adhesion Kinase; MDA-MB-231 Breast cancer cells; Pentoxifylline; Proliferation; RhoGTPases