title: Lopinavir shows greater specificity than zinc finger ejecting compounds as a potential treatment for human papillomavirus-related lesions.
abstract: Non-surgical, antiviral treatment options are desirable for HPV-related lesions within the genitourinary and upper digestive tract. We compared the toxicity of three zinc finger-ejecting (ZFE) compounds (4,4-dithiodimorpholine, azodicarbonamide, and diamide) to the HIV protease inhibitor lopinavir using HPV-positive SiHa, CaSki, HeLa, ME180, and HPV-negative C33A cervical carcinoma cell lines as well as primary human foreskin keratinocytes (PHFKs). Colorimetric growth assays revealed selective toxicity when treated with lopinavir. All carcinoma cell lines, except CaSki, were sensitive to 20 μM lopinavir whereas primary PHFKs were highly resistant. In contrast, 4,4-dithiodimorpholine was uniformly toxic to all cells tested while azodicarbonamide and diamide showed no effect at all. It is concluded that lopinavir may be an attractive candidate to treat pre-cancerous and cancerous HPV-positive lesions.
authors.affiliation: Probe Development and Biomarker Exploration, Thunder Bay Regional Research Institute, Thunder Bay, Ontario, Canada. zehbei@tbh.net
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Zehbe
authors.forename: Christina
authors.initials: C
authors.lastname: Richard
authors.forename: Kyle F
authors.initials: KF
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Campbell
authors.forename: Lynne
authors.initials: L
authors.lastname: Hampson
authors.forename: Ian N
authors.initials: IN
authors.lastname: Hampson
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001391:Azo Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003958:Diamide / Q000494:pharmacology*; D005260:Female; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes; D007928:Lethal Dose 50; D061466:Lopinavir; D008826:Microbial Sensitivity Tests; D009025:Morpholines / Q000494:pharmacology*; D027383:Papillomaviridae / Q000187:drug effects*; D030361:Papillomavirus Infections / Q000188:drug therapy; D011744:Pyrimidinones / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D001391:Azo Compounds; D017320:HIV Protease Inhibitors; D009025:Morpholines; D011744:Pyrimidinones; D003958:Diamide; D061466:Lopinavir; C004525:azodicarbonamide; C013975:4,4'-dithiodimorpholine