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Study of in vitro and in vivo effects of 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantane (DPD), a novel cytostatic and differentiation inducing agent, on human colon cancer cells.

Wang JJ, Chang YF, Chern YT, Chi CW - Br. J. Cancer (2003)

Bottom Line: The expression of cyclin D was decreased in DPD-treated cells.The in vivo effect of tumour growth suppression by DPD was also observed in mouse xenografts.These results suggest that DPD appears to be a new potentially less toxic modality of cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: National Taipei College of Nursing, 365 Ming Te Road, Taipei 11219, Taiwan. ccwang@ntcn.edu.tw

ABSTRACT
A diamantane derivative 1,6-Bis [4-(4-amino-3-hydroxyphenoxy) phenyl] diamantane (DPD) was found to inhibit the growth of several cancer cell lines in the National Cancer Institute (NCI) Anticancer Drug Screen system. In this study, we examined the in vitro and in vivo effects of DPD on human colon cancer cells. DPD exerted growth inhibitory activities in vitro against three human colon cancer cell lines (Colo 205, HT-29, and HCT-15). DPD-treated cells were arrested at G(0)/G(1) as analysed by flow cytometric analysis. The expression of cyclin D was decreased in DPD-treated cells. The differentiation markers of carcinoembryonic antigen and fibronectin were significantly increased in colon cancer cells after treatment with DPD. The epithelium-like brush borders on HT-29 cell surface were also demonstrated at 1 week after withdrawal from DPD treatment. The DPD-induced cell growth inhibition and differentiation were irreversible after removal of DPD. The in vivo effect of tumour growth suppression by DPD was also observed in mouse xenografts. No acute toxicity was observed after an intraperitoneal challenge of DPD in BALB/c-nude mice weekly. These results suggest that DPD appears to be a new potentially less toxic modality of cancer therapy.

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The effect of DPD on cell cycle arrest at day 3 in three colon cancer cell lines. Cells were seeded at 5 × 105 cells per 60 mm or 1 × 106 cells per 100 mm dish in growth medium. At the following day the cells were replenished with medium containing 1, 2, or 4 μM DPD. Cells were harvested and the cell cycle was analysed by flow cytometry as described in ‘Materials and Methods’. (A) The representative cell cycle progression in DPD-treated colon cancer cell lines. (B) The mean percentages of G0/G1, S and G2/M cells in DPD-treated colon cancer cell lines. Data are shown as the mean±s.e. of mean of duplicate samples from one of two independent experiments.
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fig2: The effect of DPD on cell cycle arrest at day 3 in three colon cancer cell lines. Cells were seeded at 5 × 105 cells per 60 mm or 1 × 106 cells per 100 mm dish in growth medium. At the following day the cells were replenished with medium containing 1, 2, or 4 μM DPD. Cells were harvested and the cell cycle was analysed by flow cytometry as described in ‘Materials and Methods’. (A) The representative cell cycle progression in DPD-treated colon cancer cell lines. (B) The mean percentages of G0/G1, S and G2/M cells in DPD-treated colon cancer cell lines. Data are shown as the mean±s.e. of mean of duplicate samples from one of two independent experiments.

Mentions: The cell cycle progression of Colo205, HT-29 and HCT-15 cells was examined using flow cytometry after exposure to 1, 2, or 4 μM DPD for 72 h (Figure 2AFigure 2


Study of in vitro and in vivo effects of 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantane (DPD), a novel cytostatic and differentiation inducing agent, on human colon cancer cells.

Wang JJ, Chang YF, Chern YT, Chi CW - Br. J. Cancer (2003)

The effect of DPD on cell cycle arrest at day 3 in three colon cancer cell lines. Cells were seeded at 5 × 105 cells per 60 mm or 1 × 106 cells per 100 mm dish in growth medium. At the following day the cells were replenished with medium containing 1, 2, or 4 μM DPD. Cells were harvested and the cell cycle was analysed by flow cytometry as described in ‘Materials and Methods’. (A) The representative cell cycle progression in DPD-treated colon cancer cell lines. (B) The mean percentages of G0/G1, S and G2/M cells in DPD-treated colon cancer cell lines. Data are shown as the mean±s.e. of mean of duplicate samples from one of two independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2394436&req=5

fig2: The effect of DPD on cell cycle arrest at day 3 in three colon cancer cell lines. Cells were seeded at 5 × 105 cells per 60 mm or 1 × 106 cells per 100 mm dish in growth medium. At the following day the cells were replenished with medium containing 1, 2, or 4 μM DPD. Cells were harvested and the cell cycle was analysed by flow cytometry as described in ‘Materials and Methods’. (A) The representative cell cycle progression in DPD-treated colon cancer cell lines. (B) The mean percentages of G0/G1, S and G2/M cells in DPD-treated colon cancer cell lines. Data are shown as the mean±s.e. of mean of duplicate samples from one of two independent experiments.
Mentions: The cell cycle progression of Colo205, HT-29 and HCT-15 cells was examined using flow cytometry after exposure to 1, 2, or 4 μM DPD for 72 h (Figure 2AFigure 2

Bottom Line: The expression of cyclin D was decreased in DPD-treated cells.The in vivo effect of tumour growth suppression by DPD was also observed in mouse xenografts.These results suggest that DPD appears to be a new potentially less toxic modality of cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: National Taipei College of Nursing, 365 Ming Te Road, Taipei 11219, Taiwan. ccwang@ntcn.edu.tw

ABSTRACT
A diamantane derivative 1,6-Bis [4-(4-amino-3-hydroxyphenoxy) phenyl] diamantane (DPD) was found to inhibit the growth of several cancer cell lines in the National Cancer Institute (NCI) Anticancer Drug Screen system. In this study, we examined the in vitro and in vivo effects of DPD on human colon cancer cells. DPD exerted growth inhibitory activities in vitro against three human colon cancer cell lines (Colo 205, HT-29, and HCT-15). DPD-treated cells were arrested at G(0)/G(1) as analysed by flow cytometric analysis. The expression of cyclin D was decreased in DPD-treated cells. The differentiation markers of carcinoembryonic antigen and fibronectin were significantly increased in colon cancer cells after treatment with DPD. The epithelium-like brush borders on HT-29 cell surface were also demonstrated at 1 week after withdrawal from DPD treatment. The DPD-induced cell growth inhibition and differentiation were irreversible after removal of DPD. The in vivo effect of tumour growth suppression by DPD was also observed in mouse xenografts. No acute toxicity was observed after an intraperitoneal challenge of DPD in BALB/c-nude mice weekly. These results suggest that DPD appears to be a new potentially less toxic modality of cancer therapy.

Show MeSH
Related in: MedlinePlus