title: Repositioning of anti-viral drugs as therapy for cervical cancer.
abstract: BACKGROUND
  Increase in expression of eIF4E (Eukaryotic translation initiation factor 4E) protein is mediated by oncogenic proteins of Human Papilloma Virus (HPV). Increased expression of eIF4E plays an important role in HPV induced carcinogenesis. Ribavirin and Indinavir are known inhibitors of eIF4E activity.
  
  
  METHODS
  The effect of the drugs on HeLa cells was assessed by in vitro assays including cell viability using MTT and Neutral red assay, apoptotic potential using Caspase-3, Caspase-8 and Caspase-9 activity assays and MMP-2 and MMP-9 secretion by determination of Gelatinase activity. The in vivo effect of Ribavirin treatment on tumor volume was assessed in human xenograft in immunocompromised C57BL/6 mice.
  
  
  RESULTS
  In vitro analyses indicate that Ribavirin and Indinavir reduce viability of HeLa cells, induce apoptosis and decrease secretion of MMPs. Treatment with Ribavirin at a dose of 50mg/kg and 100mg/kg daily led to significant decrease in tumor volume in vivo.
  
  
  CONCLUSIONS
  The study thus provides evidence that Ribavirin and Indinavir can be explored as therapy against HPV-18 induced cervical cancer.
authors.affiliation: Department of Pharmacology and Toxicology, NIPER-Ahmedabad, C/o B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Thaltej, Thaltej-Gandhinagar Highway, Ahmedabad 380054, Gujarat, India.
authors.forename: Sapna
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Thaltej, Thaltej-Gandhinagar Highway, Ahmedabad 380054, Gujarat, India.
authors.forename: Ruma
authors.initials: R
authors.lastname: Baksi
authors.affiliation: Department of Pharmacology and Toxicology, NIPER-Ahmedabad, C/o B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Thaltej, Thaltej-Gandhinagar Highway, Ahmedabad 380054, Gujarat, India; Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Thaltej, Thaltej-Gandhinagar Highway, Ahmedabad 380054, Gujarat, India. Electronic address: milee.agarwal@yahoo.com.
authors.forename: Milee
authors.initials: M
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D058492:Drug Repositioning / Q000379:methods; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D000998:Antiviral Agents; D020169:Caspases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: HPV; HeLa; Indinavir; Ribavirin