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| 題名: | 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 |
| 作者: | Wang, JJ (Wang, Jane-Jen)
Hung, HF (Hung, Hui-Fang)
Huang, ML (Huang, Min-Li)
Lee, HJ (Lee, Hui-Ju)
Chern, YT (Chern, Yaw-Terng)
Chang, YF (Chang, Yuh-Fang)
Chi, CW (Chi, Chin-Wen)
Hsu, YC (Hsu, Yi-Chiung) |
| 貢獻者: | Dept Hort & Biotechnol |
| 關鍵詞: | colorectal carcinoma
cell cycle
p21
anti-proliferation
anti-migration
diamantane |
| 日期: | 2012-03 |
| 上傳時間: | 2013-02-22 16:16:36 (UTC+8) |
| 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 G(0)/G(1) 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 G(0)/G(1), 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 G(0)/G(1), 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. |
| 關聯: | ONCOLOGY REPORTS 卷: 27 期: 2 頁數: 529-534 |
| 顯示於類別: | [園藝暨生物技術學系] 期刊論文
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