title: Imiquimod Induces Apoptosis in Human Endometrial Cancer Cells In vitro and Prevents Tumor Progression In vivo.
abstract: The increasing incidence of endometrial cancer (EC), in younger age at diagnosis, calls for new tissue-sparing treatment options. This work aims to evaluate the potential of imiquimod (IQ) in the treatment of low-grade EC.
  
  
  
  Effects of IQ on the viabilities of Ishikawa and HEC-1A cells were evaluated using MTT assay. The ability of IQ to induce apoptosis was evaluated by testing changes in caspase 3/7 levels and expression of cleaved caspase-3, using luminescence assay and western blot. Apoptosis was confirmed by flow cytometry and the expression of cleaved PARP. Western blot was used to evaluate the effect of IQ on expression levels of Bcl-2, Bcl-xL, and BAX. Finally, the in vivo efficacy of IQ was tested in an EC mouse model.
  
  
  
  There was a decrease in EC cell viability following IQ treatment as well as increased caspase 3/7 activities, cleaved caspase-3 expression, and Annexin-V/ 7AAD positive cell population. Western blot results showed the ability of IQ in cleaving PARP, decreasing Bcl-2 and Bcl-xL expressions, but not affecting BAX expression. In vivo study demonstrated IQ's ability to inhibit EC tumor growth and progression without significant toxicity.
  
  
  
  IQ induces apoptosis in low-grade EC cells in vitro, probably through its direct effect on Bcl-2 family protein expression. In, vivo, IQ attenuates EC tumor growth and progression, without an obvious toxicity. Our study provides the first building block for the potential role of IQ in the non-surgical management of low-grades EC and encouraging further investigations.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Utah, Salt Lake City, UT, 84132, USA.|Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112, USA.
authors.forename: Aliyah
authors.initials: A
authors.lastname: Almomen
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Utah, Salt Lake City, UT, 84132, USA.|Department of Pathology, University of Utah, Salt Lake City, UT, 84112, USA.
authors.forename: Elke A
authors.initials: EA
authors.lastname: Jarboe
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Utah, Salt Lake City, UT, 84132, USA.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Dodson
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Utah, Salt Lake City, UT, 84132, USA.
authors.forename: C Matthew
authors.initials: CM
authors.lastname: Peterson
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112, USA.
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Owen
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Utah, Salt Lake City, UT, 84132, USA. margit.janat-amsbury@hsc.utah.edu.|Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112, USA. margit.janat-amsbury@hsc.utah.edu.
authors.forename: Margit M
authors.initials: MM
authors.lastname: Janát-Amsbury
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D000077271:Imiquimod; D051379:Mice; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D017304:Annexin A5; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053179:Caspase 7; D000077271:Imiquimod
keywords: Bcl-2; apoptosis; cleaved PARP; endometrial cancer; imiquimod