title: Combined Parthenolide and Balsalazide Have Enhanced Antitumor Efficacy Through Blockade of NF-κB Activation.
abstract: Balsalazide is a colon-specific prodrug of 5-aminosalicylate that is associated with a reduced risk of colon cancer in patients with ulcerative colitis. Parthenolide, a strong NF-κB inhibitor, has recently been demonstrated to be a promising therapeutic agent, promoting apoptosis of cancer cells. In the current study, the antitumor effect of balsalazide combined with parthenolide in human colorectal cancer cells and colitis-associated colon cancers (CAC) was investigated. The results demonstrate that the combination of balsalazide and parthenolide markedly suppress proliferation, nuclear translocation of NF-κB, IκB-α phosphorylation, NF-κB DNA binding, and expression of NF-κB targets. Apoptosis via NF-κB signaling was confirmed by detecting expression of caspases, p53 and PARP. Moreover, treatment of a CAC murine model with parthenolide and balsalazide together resulted in significant recovery of body weight and improvement in histologic severity. Administration of parthenolide and balsalazide to CAC mice also suppressed carcinogenesis as demonstrated by uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) using micro-PET/CT scans. These results demonstrate that parthenolide potentiates the efficacy of balsalazide through synergistic inhibition of NF-κB activation and the combination of dual agents prevents colon carcinogenesis from chronic inflammation.
  
  
  
  This study represents the first evidence that combination therapy with balsalazide and parthenolide could be a new regimen for colorectal cancer treatment. Mol Cancer Res; 15(2); 141-51. ©2016 AACR.
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Se-Lim
authors.initials: SL
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Seong Hun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Young Ran
authors.initials: YR
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Department of Pathology, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Yo Na
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Seung Young
authors.initials: SY
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: In Hee
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Seung Ok
authors.initials: SO
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors.forename: Soo Teik
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea. clickm@jbnu.ac.kr.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004357:Drug Synergism; D005260:Female; D006801:Humans; D019804:Mesalamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010659:Phenylhydrazines / Q000008:administration & dosage / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D010659:Phenylhydrazines; D012717:Sesquiterpenes; C002669:parthenolide; D019804:Mesalamine; C038637:balsalazide