title: The Effects of Histone Deacetylase Inhibitor and Calpain Inhibitor Combination Therapies on Ovarian Cancer Cells.
abstract: Ovarian cancer is difficult to treat due to absence of selective drugs and tendency of platinum drugs to promote resistance. Combination therapy using epigenetic drugs is predicted to be a beneficial alternative.
  
  
  
  This study investigated the effects of combination therapies using two structurally different histone deacetylase (HDAC) inhibitors (HDACi), sodium butyrate and suberanilohydroxamic acid (SAHA), with the calpain inhibitor calpeptin on two characteristically different ovarian cancer cell lines, CAOV-3 and SKOV-3.
  
  
  
  Suboptimal doses of HDACi and calpeptin produced several effects. Growth inhibition was enhanced and the epigenetically silenced tumor suppressor genes ARHI, p21 and RARβ2 were re-expressed. Methylation of specific CpG residues in ARHI were reduced. Cell-cycle progression was inhibited and apoptosis, as well as autophagy, were induced. The phosphorylation of ERK and Akt were differentially effected by these inhibitors.
  
  
  
  The re-expression of tumor suppressors may sensitize ovarian cancer cells, which then undergo apoptosis and autophagy for cell death.
authors: Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A.|Quinnipiac University School of Medicine, North Haven, CT, U.S.A.
authors: Karolina
authors: K
authors: Lapinska
authors: School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, U.S.A.
authors: Genevieve
authors: G
authors: Housman
authors: Department of Pediatrics, Children's Hospital/Harvard Medical School, Boston, MA, U.S.A.
authors: Shannon
authors: S
authors: Byler
authors: Vanderbilt University School of Medicine, Nashville, TN, U.S.A.
authors: Sarah
authors: S
authors: Heerboth
authors: Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A.
authors: Amber
authors: A
authors: Willbanks
authors: Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A.
authors: Anuja
authors: A
authors: Oza
authors: Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A. ssarkarmmb@gmail.com.|Genome Science Institute, Boston University School of Medicine, Boston, MA, U.S.A.
authors: Sibaji
authors: S
authors: Sarkar
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*
chemical_list: D006023:Glycoproteins; D056572:Histone Deacetylase Inhibitors; C039304:calpain inhibitors
keywords: Ovarian cancer; apoptosis; autophagy; calpain; cell cycle; combination therapy; epigenetic drugs; histone deacetylase inhibitors; methylation