Induction of growth inhibition and G1 arrest in human cancer cell lines by relatively low-toxic diamantane derivatives

Wang, Jane-Jen; Huang, Kuo-Tong; Chern, Yaw-Terng

doi:10.1097/00001813-200403000-00013

Cited by 15 publications

(13 citation statements)

References 17 publications

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“…The anti-proliferative effects and differentiation-inducing property of DPD were demonstrated in human colon cancer cells (12). DPD also induced G 1 arrest in Colo 205 cells and this effect was irreversible after removal of DPD (11). In addition, we also examined the in vivo therapeutic potential of DPD in Colo 205 cell xenografts.…”

Section: Introductionmentioning

confidence: 97%

“…In our previous studies, we had characterized the anticancer activities of adamantane and diamantane derivatives using the 60 human cancer cell lines in the NCI Anticancer Drug Screen and evaluated the structure-activity relationship. The diamantane derivative 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane (DPD) exhibited marked anticancer activities on colon cancer (Colo 205), leukemia (HL-60), non-small cell lung cancer (HOP-92), ovarian cancer (OVCAR-8) and breast cancer (T-47D) cell lines (11). The anti-proliferative effects and differentiation-inducing property of DPD were demonstrated in human colon cancer cells (12).…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2011

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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 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 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.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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“…1, 6-Bis [4-(4-amino-3-hydroxyphenoxy) phenyl] diamantane (DPD) exhibited marked anticancer activity on the sub-panel of 60 human cancer cell lines (5). The antiproliferative effects and differentiation-inducing property of DPD were demonstrated in human colon cancer cells, and the DPD-induced effects were irreversible after removal of DPD (6).…”

Section: Introductionmentioning

confidence: 99%

The antitumor effect of a novel differentiation inducer, 2, 2-Bis (4-(4-amino-3-hydroxyphenoxy) phenyl) adamantane (DPA), in combinatory therapy on human colon cancer

Wang

Lee²,

Chen³

et al. 2006

Int J Oncol

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Abstract. An adamantane derivative, 2, 2-Bis (4-(4-amino-3-hydroxyphenoxy) phenyl) adamantane (DPA), was found to inhibit the growth of several cancer cell lines in the National Cancer Institute (NCI) Anticancer Drug Screen system. Our previous study showed that DPA inhibited the growth of human colon cancer cell Colo 205 xenografts. DPAtreated cells were arrested at G 0 /G 1 , and the DPA-induced cell growth inhibition was irreversible after removal of DPA. Moreover, no acute toxicity was observed after an intraperitoneal challenge of DPA in nude mice weekly. In this study, we examined the in vivo therapeutic potential of DPA combined with clinical chemotherapeutic agent CPT-11 in Colo 205 cell xenografts. The in vitro cytostatic and differentiative effects of DPA on human colon cancer cells was also evaluated. DPA exerted growth inhibitory activities in vitro against three human colon cancer cell lines (Colo 205, HT-29, and HCT-15). DPA-treated cells showed a more adhesive epithelial phenotype. The differentiation markers of carcinoembryonic antigen (CEA) and fibronectin (FN) were significantly increased in colon cancer cells after treatment with DPA. Further studies showed the induction of p21/Cip1, p27/Kip1, E-cadherin and dephosphorylated p120ctn expression was involved in DPA-induced anticancer effects. Interestingly, DPA-induced elevation of p21/Cip1 was independent of the induction of p53 in Colo 205 cells. In vivo results demonstrated that DPA enhanced the in vivo anticancer activity of the chemotherapeutic agent, CPT-11, by elevation of p53-independent p21/Cip1 and p27/Kip1 expression. Our results suggest that DPA appears to be a new potentially less toxic modality of cancer combinatory therapy.

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“…A previous study characterized the anticancer activities of diamantane derivatives using 60 human cancer cell lines in the National Cancer Institute (NCI) Anticancer Drug Screening, and evaluated the structure-activity association. 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane (DPD) demonstrated significant anticancer activity on the sub-panel of cell lines (16). The antiproliferative and differentiation-inducing effects of DPD were observed in human colon cancer cells, and these effects were irreversible following the removal of DPD (17).…”

Section: 6-bis[4-(4-amino-3-hydroxyphenoxy)phenyl] Diamantanementioning

confidence: 99%

1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane potentiates in vitro and in vivo antitumor effects of irinotecan on human colorectal cancer cells

Yang

Wang

et al. 2016

Oncology Letters

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Abstract. 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane (DPD), a diamantane derivative, was previously noted as an anticancer compound through anticancer drug screening with NCI-60 human tumor cells. Irinotecan (CPT-11), a semisynthetic derivative of camptothecin, is clinically active in the treatment of colorectal cancer, with no cross-resistance. The current study conducted a pharmacokinetic evaluation of DPD, an essential component of drug discovery. Subsequent pathway analysis of microarray gene expression data indicated that the anticancer mechanisms of DPD were associated with cell cycle progression and apoptosis. The combined effect of DPD and CPT-11 with regard to the mechanisms of apoptosis-related pathways in COLO 205 cells, and the antitumor effects in colon cancer xenograft mice, were investigated. The plasma concentration and pharmacokinetic parameters of DPD in male albino rats were analyzed following a single dose of DPD by injection. The protein expression of active caspase-3, procaspase-3 and poly ADP-ribose polymerase (PARP) in COLO 205 cells treated with DPD and CPT-11, alone or combined, was evaluated by western blotting. A trypan blue dye exclusion assay revealed that, whilst DPD alone demonstrated good antitumor effects, this effect was potentiated when combined with CPT-11. Combined treatment with DPD and CPT-11 upregulated the expression of cleaved PARP, procaspase-3, caspase-3 and active caspase-3 in COLO 205 cells. In the colon cancer xenograft model, compared with the control (vehicle-treated) mice, the sizes of the tumors were significantly lower in mice treated with DPD and CPT-11, alone or in combination. Thus, DPD may be a potential therapeutic agent for the treatment of colorectal cancer via upregulating apoptosis-related pathways.

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Induction of growth inhibition and G1 arrest in human cancer cell lines by relatively low-toxic diamantane derivatives

Cited by 15 publications

References 17 publications

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

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

The antitumor effect of a novel differentiation inducer, 2, 2-Bis (4-(4-amino-3-hydroxyphenoxy) phenyl) adamantane (DPA), in combinatory therapy on human colon cancer

1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane potentiates in vitro and in vivo antitumor effects of irinotecan on human colorectal cancer cells

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