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|Ref Type||Journal Article|
|Authors||Kim SL, Kim SH, Park YR, Liu YC, Kim EM, Jeong HJ, Kim YN, Seo SY, Kim IH, Lee SO, Lee ST, Kim SW|
|Title||Combined Parthenolide and Balsalazide Have Enhanced Antitumor Efficacy Through Blockade of NF-κB Activation.|
|Journal||Molecular cancer research : MCR|
|Abstract Text||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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Balsalazide||Carbadox||Balsalazida||Carbadox (balsalazide) is a 5-aminosalicylate (5-ASA) type drug that is FDA approved for the treatment of inflammation resulting from ulcerative colitis (FDA.gov), however, has also been demonstrated to induce apoptosis and decrease cell proliferation in cancer cells (PMID: 28108625).|
|Parthenolide||Parthenolide is derived from Tanacetum parthenium and is an inhibitor of NF-kB and IL-1, which potentially results in apoptosis by blocking the activation of NF-kB in cancer cells (PMID: 21603970, PMID: 28108625, PMID: 32742599, PMID: 32705224).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||colorectal cancer||not applicable||Balsalazide + Parthenolide||Preclinical - Cell culture||Actionable||In a preclinical study, the combination of Balsalazide and Parthenolide resulted in a synergistic effect, resulting in reduced cell viability and increased apoptotic activity in colorectal cancer cells in culture (PMID: 28108625).||28108625|