title: Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer.
abstract: BACKGROUND
  Despite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if the survival rate is to be improved. Epidemiologic studies have suggested a protective effect from certain plant-derived foods and extracts; however, it has been difficult to isolate and identify the compounds most responsible for these observations. The primary purpose of this study was to investigate the response of human oral squamous cell carcinoma (OSCC) to proanthocyanidin (PAC), a plant-derived compound that may inhibit the progression of several other cancers.
  
  
  METHODS
  Using a series of in vitro assays, we sought to quantify the effects of PAC on OSCC, cervical carcinoma, and non-cancerous cell lines, specifically the effects of PAC on cell proliferation. Recent data suggest that infection with the human papillomavirus (HPV) may also modulate the proliferative potential of OSCC; therefore, we also measured the effects of PAC administration on HPV-transfected OSCC proliferation.
  
  
  RESULTS
  Our results demonstrated that PAC administration was sufficient to significantly suppress cellular proliferation of OSCC in a dose-dependent manner. In addition, the increased proliferation of OSCC after transfection with HPV 16 was reduced by the administration of PAC, as was the proliferation of the cervical cancer and non-cancerous cell lines tested. Our results also provide preliminary evidence that PAC administration may induce apoptosis in cervical and oral cancer cell lines, while acting merely to suppress proliferation of the normal cell line control.
  
  
  CONCLUSIONS
  These results signify that PAC may be a compelling candidate for testing in both animal and human models. Furthermore, these data provide adequate justification for elucidating the divergent mechanisms of PAC-induced proliferation, inhibition, and apoptosis among these and other cell lines.
authors.affiliation: Department of Biomedical Sciences, School of Dental Medicine, University of Nevada, Las Vegas, USA. michael.king@sdm.unlv.edu <michael.king@sdm.unlv.edu>
authors.forename: Michael
authors.initials: M
authors.lastname: King
authors.forename: Kourt
authors.initials: K
authors.lastname: Chatelain
authors.forename: Dustin
authors.initials: D
authors.lastname: Farris
authors.forename: Dayne
authors.initials: D
authors.lastname: Jensen
authors.forename: Jason
authors.initials: J
authors.lastname: Pickup
authors.forename: Aaron
authors.initials: A
authors.lastname: Swapp
authors.forename: Susan
authors.initials: S
authors.lastname: O'Malley
authors.forename: Karl
authors.initials: K
authors.lastname: Kingsley
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D052162:Human papillomavirus 16; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics; D030361:Papillomavirus Infections / Q000188:drug therapy; D010641:Phenotype; D044945:Proanthocyanidins / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
chemical_list: D044945:Proanthocyanidins