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https://doi.org/10.18632/oncotarget.5385
| Title: | PRIMA-1met (APR-246) inhibits growth of colorectal cancer cells with different p53 status through distinct mechanisms | Authors: | Li, X.-L Zhou, J Chan, Z.-L Chooi, J.-Y Chen, Z.-R Chng, W.-J |
Keywords: | antineoplastic agent prima 1 met protein Noxa protein p53 PUMA protein unclassified drug 2-hydroxymethyl-2-methoxymethylazabicyclo(2.2.2)octan-3-one protein p53 quinuclidine derivative TP53 protein, human animal experiment animal model apoptosis Article cancer growth cancer inhibition cell migration cell proliferation clinical effectiveness colony formation colorectal cancer controlled study dose response female human human cell mouse nonhuman protein expression treatment duration treatment response upregulation animal Caco-2 cell line Colorectal Neoplasms disease model drug effects drug screening genetics HT-29 cell line metabolism nonobese diabetic mouse pathology SCID mouse Animals Caco-2 Cells Cell Proliferation Colorectal Neoplasms Disease Models, Animal HT29 Cells Humans Mice Mice, Inbred NOD Mice, SCID Quinuclidines Tumor Suppressor Protein p53 Xenograft Model Antitumor Assays |
Issue Date: | 2015 | Citation: | Li, X.-L, Zhou, J, Chan, Z.-L, Chooi, J.-Y, Chen, Z.-R, Chng, W.-J (2015). PRIMA-1met (APR-246) inhibits growth of colorectal cancer cells with different p53 status through distinct mechanisms. Oncotarget 6 (34) : 36689-36699. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.5385 | Abstract: | PRIMA-1met (APR-246) is a methylated derivative and structural analog of PRIMA-1 (p53 re-activation and induction of massive apoptosis). PRIMA-1met has been reported to restore both the wild type (wt) structure and function of mutant p53. Here, we show that PRIMA-1met is highly effective at limiting the growth of CRC cells regardless of p53 status. However, PRIMA-1met induces robust apoptosis only in CRC cells with mutant p53. Upregulation of Noxa, a proapoptotic molecule, is crucial for PRIMA-1met mediated activity. In human xenograft model of disease, PRIMA-1met effectively suppresses CRC tumor growth. Our results uncover distinct mechanisms of PRIMA-1met in CRC with different p53 status, thus providing a mechanistic rationale to evaluate the clinical efficacy of PRIMA-1met in CRC patients with different p53 status. | Source Title: | Oncotarget | URI: | https://scholarbank.nus.edu.sg/handle/10635/174132 | ISSN: | 19492553 | DOI: | 10.18632/oncotarget.5385 |
| Appears in Collections: | Elements Staff Publications |
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