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

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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
Authors:	許藝瓊;Chi, Chin-Wen
Contributors:	生醫理工學院生醫科學與工程學系
Keywords:	Adamantane;Adamantane - analogs & derivatives;Adamantane - pharmacology;Animals;Antineoplastic Agents;Antineoplastic Agents - pharmacology;Antineoplastic Agents - therapeutic use;Biological and medical sciences;Carcinoma;Carcinoma - drug therapy;Carcinoma - genetics;Carcinoma - metabolism;Cell Cycle;Cell Cycle - drug effects;Cell Line, Tumor;Cell Movement;Cell Movement - drug effects;Cell Movement - genetics;Cell Proliferation;Cell Proliferation - drug effects;Colonic Neoplasms;Colonic Neoplasms - drug therapy;Colonic Neoplasms - genetics;Colonic Neoplasms - metabolism;Cyclin-Dependent Kinase Inhibitor p21;Cyclin-Dependent Kinase Inhibitor p21 - genetics;Cyclin-Dependent Kinase Inhibitor p21 - metabolism;Gastroenterology. Liver. Pancreas. Abdomen;HCT116 Cells;Humans;Male;Medical sciences;Mice;Mice, Inbred BALB C;Mice, Nude;Signal Transduction;Signal Transduction - drug effects;Stomach. Duodenum. Small intestine. Colon. Rectum. Anus;Tumor Suppressor Protein p53;Tumor Suppressor Protein p53 - genetics;Tumor Suppressor Protein p53 - metabolism;Tumors
Date:	2012-02-01
Issue Date:	2026-04-23 11:20:23 (UTC+8)
Publisher:	Spandidos Publications;Athens: Spandidos Publications
Abstract:	摘要： 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. 其他題名： Oncol Rep 出版者： Athens: Spandidos Publications 出版日期： 2012-02-01 出處： Oncology Reports, 2012-02, Vol.27 (2), p.529-534 版權： 2015 INIST-CNRS 識別號： ISSN: 1021-335X 識別號： ISSN: 1791-2431 識別號： EISSN: 1791-2431 識別號： DOI: 10.3892/or.2011.1546 識別號： PMID: 22076474
Appears in Collections:	[Department of Biomedical Sciences and Engineering ] journal & Dissertation

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