title: Enhanced antitumor effect of combination therapy with gemcitabine and guggulsterone in pancreatic cancer.
abstract: OBJECTIVE
  Guggulsterone is a dietary plant sterone possessing therapeutic potential against cancers. However, the antitumor effect of this natural compound on pancreatic cancer has not been determined yet. This study was designed to investigate the therapeutic efficacy of guggulsterone in pancreatic cancer.
  
  
  METHODS
  In this study, we examined the effect of guggulsterone on cell proliferation and apoptosis in pancreatic cancer cell lines, and then, we investigated the mechanisms responsible for the effect of guggulsterone. Finally, we investigated whether the combination of guggulsterone and gemcitabine had an additional therapeutic effect compared to gemcitabine single regimen in pancreatic cancer cell lines (in vitro) and in a xenograft model using nude mice (in vivo).
  
  
  RESULTS
  In vitro, the combination treatment resulted in more growth inhibition and apoptosis through the down-regulation of nuclear factor κB activity with suppression of Akt and BcL-2 and through the activation of c-Jun NH(2)-terminal kinase and Bax in pancreatic cancer cell lines. In vivo, the combination therapy augmented tumor growth inhibition through the same mechanisms in tumor tissue.
  
  
  CONCLUSIONS
  The combination of guggulsterone to gemcitabine enhanced antitumor efficacy through apoptosis induction by suppressing Akt and nuclear factor κB activity and by modulating apoptosis-related protein expression in pancreatic cancer.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Ahn
authors.forename: Jeong Kyun
authors.initials: JK
authors.lastname: Seo
authors.forename: Sang Hyub
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Hwang
authors.forename: Jun Kyu
authors.initials: JK
authors.lastname: Lee
authors.forename: Ji Kon
authors.initials: JK
authors.lastname: Ryu
authors.forename: Yong-Tae
authors.initials: YT
authors.lastname: Kim
authors.forename: Yong Bum
authors.initials: YB
authors.lastname: Yoon
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004357:Drug Synergism; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011282:Pregnenediones / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D011282:Pregnenediones; D003841:Deoxycytidine; D004247:DNA; C023617:pregna-4,17-diene-3,16-dione; D051058:Oncogene Protein v-akt; D000093542:Gemcitabine