title: CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo.
abstract: Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Small molecule CP-31398 was shown to restore mutant p53 tumor suppressor functions in cancer cells. Here, we determined the effects of CP-31398 on the growth of p53-mutated colorectal cancer (CRC) cells in vitro and in vivo. CRC cells which carry p53 mutation in codon 273 were treated with CP-31398 and the control, and the effects of CP-31398 on cell cycle, cell apoptosis, and proliferation were determined. The expression of p53-responsive downstream genes was evaluated by quantitative reverse transcriptase PCR (RT-PCR) and Western blot. CP-31398 was administrated into xenograft tumors created by the inoculation of HT-29 cells, and then the effect of CP-31398 on the growth of xenograft tumors was examined. CP-31398 induced p53 downstream target molecules in cultured HT-29 cells, which resulted in the inhibition of CRC cell growth assessed by the determination of cell cycle, apoptosis, and cell proliferation. In xenograft tumors, CP-31398 modulated the expression of Bax, Bcl-2, caspase 3, cyclin D, and Mdm2 and then blocked the growth of xenograft tumors. CP-31398 would be developed as a therapeutic candidate for p53-mutated CRC due to the restoration of mutant p53 tumor suppressor functions.
authors: Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Xingxing
authors: X
authors: He
authors: Xinjuan
authors: X
authors: Kong
authors: Junwei
authors: J
authors: Yan
authors: Jingjun
authors: J
authors: Yan
authors: Yunan
authors: Y
authors: Zhang
authors: Qian
authors: Q
authors: Wu
authors: Ying
authors: Y
authors: Chang
authors: Haitao
authors: H
authors: Shang
authors: Qian
authors: Q
authors: Dou
authors: Yuhu
authors: Y
authors: Song
authors: Fang
authors: F
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D056741:Cyclin D / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D056741:Cyclin D; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D053148:Caspase 3; C402665:CP 31398