title: Combined Treatment with CCI779 and SB203580 Induces Cellular Senescence in Renal Cell Carcinoma Cell Line via p53 Pathway.
abstract: BACKGROUND
  Renal cell carcinoma (RCC) is one of the most common neoplasms that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In recent years, there have been significant advancements implemented to understanding the biology of RCC, which has led to the introduction of novel targeted therapies in the management of patients with metastatic disease.
  
  
  OBJECTIVE
  The present study was designed to evaluate the effects of p38 MAPK inhibitor (SB203580), alone and in combination with mTOR inhibitor (CCI779) on apoptosis and cell proliferation.
  
  
  METHODS
  Subtoxic concentrations of inhibitors were selected by MTT assay using A-498, ACHN and primary culture of RCC.
  
  
  RESULTS
  All the three types of RCC cells had almost similar response towards these inhibitors. The results revealed that 25µM of SB203580 and 20µM of CCI779 at 48 hrs decreased cell viability by 20% and 30%, respectively, whereas the combination of both inhibitors showed a maximum of 40% reduction in cell viability.
  
  
  CONCLUSIONS
  The study concludes that the combination of SB203580 and CCI779 inhibitors may induce cellular senescence in A-498 cells with higher potency than that of individual inhibitors.
authors.affiliation: Department of Urology, Postgraduate Institute of Medical Education & Research, Chandigarh-160012, India.|Department of Biotechnology, Faculty of Biomedical Sciences, Uttarakhand Ayurved University, Harrawala, Dehradun-248001, Uttarakhand, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chauhan
authors.affiliation: Department of Urology, Postgraduate Institute of Medical Education & Research, Chandigarh-160012, India.
authors.forename: Rani
authors.initials: R
authors.lastname: Ojha
authors.affiliation: Department of Phytochemistry, Faculty of Biomedical Sciences, Uttarakhand Ayurved University, Harrawala, Dehradun-248001, Uttarakhand, India.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Semwal
authors.affiliation: Uttarakhand Ayurved University, Harrawala, Dehradun-248001, Uttarakhand, India.
authors.forename: Satyendra P
authors.initials: SP
authors.lastname: Mishra
authors.affiliation: Department of Pharmaceutical Sciences, Tshwane University of Technology, Pretoria-0001, South Africa.
authors.forename: Ruchi B
authors.initials: RB
authors.lastname: Semwal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D016159:Tumor Suppressor Protein p53; C401859:temsirolimus; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D020123:Sirolimus
keywords: CCI779; Renal cell carcinoma; SB203580; apoptosis; autophagy; senescence.