Anticolorectal cancer effects and pharmacokinetic application of 2, 2-Bis [4-(4-amino-3-hydroxyphenoxy) phenyl] adamantane

NCUIR > college of Health Sciences and Technology > Department of Biomedical Sciences and Engineering > journal & Dissertation > Item 987654321/102690

Please use this identifier to cite or link to this item: https://ir.lib.ncu.edu.tw/handle/987654321/102690

Title:	Anticolorectal cancer effects and pharmacokinetic application of 2, 2-Bis [4-(4-amino-3-hydroxyphenoxy) phenyl] adamantane
Authors:	許藝瓊;Yang, Po-Sheng;Wang, Jane-Jen;Tsai, Tung-Hu;Wang, Yea-Hwey;Jan, Woan-Ching;Cheng, Shih-Ping;Chi, Chin-Wen;Hsu, Yi-Chiung
Contributors:	生醫理工學院生醫科學與工程學系
Date:	2015-09-30
Issue Date:	2026-04-23 11:15:01 (UTC+8)
Publisher:	e-Century Publishing Corporation
Abstract:	摘要： 2, 2-Bis (4-(4-amino-3-hydroxyphenoxy) phenyl) adamantane (DPA) induced growth inhibition in human cancer cells using the national cancer institute (NCI) anticancer drug screen. In our previous study, we demonstrated that DPA exerted growth inhibitory activities in the three human colon cancer cell lines (Colo 205, HT-29, and HCT-15). To identify the detailed mechanism, we examined the functional importance of p21 and p53 in DPA-induced anticancer effect. We used three isogenic colon cancer 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 DPA. DPA dose-dependently inhibited cell growth, cell migration and increased cell cycle at the G0/G1 phase in HCT116 cells but not in p21(-/-) and p53(-/-) isogenic HCT-116 cells. Additionally, Western blot showed that DPA treatment induced the p21, p53, and cyclin-E protein expressions in HCT-116 cells. The p21 associated cell cycle regulatory protein such as cyclin D, CDK4, and pRb were decreased after DPA treatment in HCT-116 cells. DPA decreased cell migration in HCT-116 and HCT-116 p53(-/-) but not in HCT-116 p21(-/-) cells. We observed the up-regulation of E-cadherin, p-p38, and p-Erk in DPA-treated HCT-116 group but not in HCT-116 p21(-/-) and HCT-116 p53(-/-) groups. We assumed that p21 was required for DPA-induced anti-colon cancer effect through the Erk and p38 pathway leading to cell cycle arrest and inhibition of cell motility. Mean (± SE) pharmacokinetic parameters of the DPA were as follows: AUC = 64.44 ± 8.41, Cmax = 1.56 ± 0.48 and t1/2 = 113.92 ± 58.19. The pharmacokinetic data suggest DPA can be applied to further clinical study. This is the first pharmacokinetic study of DPA, and indicated that anti-proliferation and the cell mobility inhibition effects of DPA in HCT116 WT cells may result from the induction of p21 through activation of ERK and p38 pathway.2, 2-Bis (4-(4-amino-3-hydroxyphenoxy) phenyl) adamantane (DPA) induced growth inhibition in human cancer cells using the national cancer institute (NCI) anticancer drug screen. In our previous study, we demonstrated that DPA exerted growth inhibitory activities in the three human colon cancer cell lines (Colo 205, HT-29, and HCT-15). To identify the detailed mechanism, we examined the functional importance of p21 and p53 in DPA-induced anticancer effect. We used three isogenic colon cancer 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 DPA. DPA dose-dependently inhibited cell growth, cell migration and increased cell cycle at the G0/G1 phase in HCT116 cells but not in p21(-/-) and p53(-/-) isogenic HCT-116 cells. Additionally, Western blot showed that DPA treatment induced the p21, p53, and cyclin-E protein expressions in HCT-116 cells. The p21 associated cell cycle regulatory protein such as cyclin D, CDK4, and pRb were decreased after DPA treatment in HCT-116 cells. DPA decreased cell migration in HCT-116 and HCT-116 p53(-/-) but not in HCT-116 p21(-/-) cells. We observed the up-regulation of E-cadherin, p-p38, and p-Erk in DPA-treated HCT-116 group but not in HCT-116 p21(-/-) and HCT-116 p53(-/-) groups. We assumed that p21 was required for DPA-induced anti-colon cancer effect through the Erk and p38 pathway leading to cell cycle arrest and inhibition of cell motility. Mean (± SE) pharmacokinetic parameters of the DPA were as follows: AUC = 64.44 ± 8.41, Cmax = 1.56 ± 0.48 and t1/2 = 113.92 ± 58.19. The pharmacokinetic data suggest DPA can be applied to further clinical study. This is the first pharmacokinetic study of DPA, and indicated that anti-proliferation and the cell mobility inhibition effects of DPA in HCT116 WT cells may result from the induction of p21 through activation of ERK and p38 pathway. 出版日期： 2015-01-01 出處： International journal of clinical and experimental medicine, 2015-01, Vol.8 (9), p.14805 識別號： ISSN: 1940-5901 識別號： EISSN: 1940-5901
Appears in Collections:	[Department of Biomedical Sciences and Engineering ] journal & Dissertation

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	26	View/Open

社群 sharing

Loading...