title: Thiazolidinediones abrogate cervical cancer growth.
abstract: Peroxisome proliferator-activated receptor gamma (PPAR γ) is activated by thiazolidinedione drugs (TZDs) and can promote anti-cancer properties. We used three TZDs (pioglitazone, rosiglitazone, and ciglitazone) to target cervical cancer cell lines and a nude mouse animal model. Each agent increased activation of PPAR γ, as judged by a luciferase reporter gene assay in three HPV-associated cell lines (CaSki, SiHa, and HeLa cells) while decreasing cellular proliferation in a dose-dependent manner. They also promoted Oil Red O accumulation in treated cell lines and upregulated the lipid differentiation marker adipsin. Interestingly, xenograft HeLa tumors in nude mice treated with 100mg/kg/day pioglitazone exhibited decreased growth compared to control mice or mice treated with standard cervical chemotherapy. In conclusion, TZDs slow tumor cell growth in vitro and in vivo with decreases in cell proliferation and increases in PPAR γ and adipsin. These agents may be interesting treatments or treatment adjuncts for HPV-associated cancers or perhaps even precancerous conditions.
authors.affiliation: Molecular Oncology Program, Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: knier003@umn.edu.
authors.forename: Beverly R
authors.initials: BR
authors.lastname: Wuertz
authors.affiliation: Molecular Oncology Program, Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: ldarrah@obgynmn.com.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Darrah
authors.affiliation: Molecular Oncology Program, Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: drwudel@drwudel.com.
authors.forename: Justin
authors.initials: J
authors.lastname: Wudel
authors.affiliation: Molecular Oncology Program, Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: ondre002@umn.edu.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Ondrey
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D011416:Complement Factor D / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D027383:Papillomaviridae / Q000187:drug effects / Q000472:pathogenicity; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C493488:CFD protein, human; D011416:Complement Factor D; C039671:ciglitazone; D000077205:Pioglitazone
keywords: Cervical cancer; Head and neck cancer; PPAR; Pioglitazone; Thiazolidinedione