title: Role of p21 as a determinant of 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]             diamantane response in human HCT-116 colon carcinoma cells.
abstract: 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantane (DPD) induces growth             inhibition in human cancer cells. In our previous study, we discovered that DPD             irreversibly inhibits the growth of Colo 205 colon cancer cells at the G0/G1 phase             and induces cell differentiation. However, the detailed mechanism is still unknown.             In this study, we examined the functional importance of p21 and p53 in DPD-induced             anticancer effects. We used three isogenic cell lines, HCT-116, HCT-116 p53-/-             and HCT-116 p21-/-, to evaluate the roles of p21 and p53 in the in vitro anticancer             effects of DPD. The in vivo anti-proliferative effect of DPD was demonstrated             by HCT-116 and HCT-116 p21-/- xenograft models. DPD significantly inhibited the             growth as well as increased the number of HCT-116 cells in the G0/G1 phase, but             not in HCT-116 p53-/- and HCT-116 p21-/- cells examined by flow cytometry. Additionally,             western blot analysis showed that DPD treatment induced p21, but not p53 protein             expression in HCT-116 cells. The p21-associated cell cycle regulated proteins,             such as cyclin D, CDK4 and pRb were decreased after DPD treatment in HCT-116 cells.             The DPD-increased G0/G1 phase and induced cell cycle regulated protein expression             were not observed in HCT-116 p21-/- and HCT-116 p53-/- cells. DPD decreased cell             migration in HCT-116 and HCT-116 p53-/- but not in HCT-116 p21-/- cells. p21 was             required for the DPD-induced in vitro anti-colon cancer effect. The in vivo study             also showed that DPD significantly inhibited tumor growth through p21 signaling.             Our results clearly demonstrate that DPD-induced in vitro and in vivo anticancer             effects through the activation of p21 in HCT-116 cells.
authors.affiliation: Center of General Education, National Taipei University of Nursing and Health Sciences, and Department of Medical Research and Educaiton, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Jane-Jen
authors.initials: JJ
authors.lastname: Wang
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Hung
authors.forename: Min-Li
authors.initials: ML
authors.lastname: Huang
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yaw-Terng
authors.initials: YT
authors.lastname: Chern
authors.forename: Yuh-Fang
authors.initials: YF
authors.lastname: Chang
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
authors.forename: Yi-Chiung
authors.initials: YC
authors.lastname: Hsu
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C480140:1,6-Bis(4-(4-amino-3-hydroxyphenoxy)phenyl)diamantane; D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D000218:Adamantane