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Dendrophthoe pentandra (L.) Miq extract effectively inhibits inflammation, proliferation and induces p53 expression on colitis-associated colon cancer

View Article: PubMed Central - PubMed

ABSTRACT

Background: Indonesian mistletoe grows on various trees. Mango Mistletoes (Dendrophthoe pentandra) is one type of mistletoe that grown on mango tree (.benalu mangga in bahasa Indonesia). Our study used mistletoe as a parasitic plant that has been used for traditional medicine. It has been known that Dendrophtoe pentandra extract (DPE) anti-inflammatory and anticancer. Furthermore, it is necessary to follow-up study in vivo to evaluate the response to treatment of new cancer therapeutic agents. This research aimed to determine the levels of IL-22, myeloperoxide (MPO), proliferation and wild-type p53 expression after the administration of DPE to murine models of CAC.

Methods: Mouse colitis associated colon cancer (CAC) was induced firstly by azoxymethane (AOM) and followed by administration of drinking water containing 5 % dextran sodium sulfate (DSS) in a cycle protocol, each cycle consisted of seven days of 5 % DSS in the drinking water and followed by seven days of regular water. This study consists of five treatment groups: I was treated water only (control), II was administrated by (DSS only, without DPE), (III-V) were administrated by DPE (125 mg/kg BW, 250 mg/kg BW and 500 mg/kg BW) respectively. The administrated of DPE were started from the 8th weeks, were continued until 21 weeks. At the end of 21 weeks of the experiment, mice were sacrificed, colon tissue was removed, and then subjected to ELISA, flow cytometry, real-time PCR and histology examination.

Results: Administration of DPE 250 mg/kgBW significantly reduce the levels of IL-22 and MPO compared with DSS only group (p < 0.001; p < 0.001). Colonic epithelial cells proliferation of group IV (DPE 250 mg/kgBW) were significantly lower than III and V groups. There was no significant change in the S phase in mice were treated DPE 125 mg/kg BW and 500 mg/kg BW, while administration of DPE 250 mg/kg BW was able to increase the percentage of cells in S phase. The expression of mRNA p53 was up regulated in mice received DPE 125 mg/kg BW.

Conclusion: These findings indicate that the DPE could inhibit colonic epithelial cells proliferation through p53 pathway independently. This study also showed that DPE could be potential sources of new therapy.

No MeSH data available.


Cell cycle analysis of colonic epithelial cells treated with or without DPE. Colon Epithelial Cells 1x106 cells were cultured in BrdU and the cells were cultivated for 24 h. (A). The harvest cells assessed with BrdU followed by labeling with a FITC conjugated anti-BrdU antibody and Propidium Iodide for the cell cycle were analyzed as described in Materials and Methods and the percentages of S phase, G0/G1 and G2/M in the areas have shown. Data are representative of four independent experiments with similar results. (B) The percentage of cells in S phase. Results shown are mean + SD, with n = 4 replicates in each group. Results are mean ± SD. *, p < 0.05. **, p < 0.001
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Fig5: Cell cycle analysis of colonic epithelial cells treated with or without DPE. Colon Epithelial Cells 1x106 cells were cultured in BrdU and the cells were cultivated for 24 h. (A). The harvest cells assessed with BrdU followed by labeling with a FITC conjugated anti-BrdU antibody and Propidium Iodide for the cell cycle were analyzed as described in Materials and Methods and the percentages of S phase, G0/G1 and G2/M in the areas have shown. Data are representative of four independent experiments with similar results. (B) The percentage of cells in S phase. Results shown are mean + SD, with n = 4 replicates in each group. Results are mean ± SD. *, p < 0.05. **, p < 0.001

Mentions: We examined whether colonic epithelial cells were resting or proliferating state. DNA synthesis was measured in colonic epithelial cells followed. The percentage of BrdU-labeled S-phase cells were determined by observing labeled cells undergoing of the S-phase of the cell cycle. Our data demonstrated that colonic epithelial cells in CAC models without DPE treatment were predominantly in S phase (45 %), in G0/G1 phase (28 %), and in G2/M (26 %). Induction of DPE treatment change the percentage of cells in S phase through not in a dose dependent manner. DPE of 125 mg/kg BW (S phase = 36 %), 250 mg/kg BW (S phase = 17 %) and 500 mg/kg BW (S phase = 30 %) (Fig. 5).Fig. 5


Dendrophthoe pentandra (L.) Miq extract effectively inhibits inflammation, proliferation and induces p53 expression on colitis-associated colon cancer
Cell cycle analysis of colonic epithelial cells treated with or without DPE. Colon Epithelial Cells 1x106 cells were cultured in BrdU and the cells were cultivated for 24 h. (A). The harvest cells assessed with BrdU followed by labeling with a FITC conjugated anti-BrdU antibody and Propidium Iodide for the cell cycle were analyzed as described in Materials and Methods and the percentages of S phase, G0/G1 and G2/M in the areas have shown. Data are representative of four independent experiments with similar results. (B) The percentage of cells in S phase. Results shown are mean + SD, with n = 4 replicates in each group. Results are mean ± SD. *, p < 0.05. **, p < 0.001
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Related In: Results  -  Collection

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Fig5: Cell cycle analysis of colonic epithelial cells treated with or without DPE. Colon Epithelial Cells 1x106 cells were cultured in BrdU and the cells were cultivated for 24 h. (A). The harvest cells assessed with BrdU followed by labeling with a FITC conjugated anti-BrdU antibody and Propidium Iodide for the cell cycle were analyzed as described in Materials and Methods and the percentages of S phase, G0/G1 and G2/M in the areas have shown. Data are representative of four independent experiments with similar results. (B) The percentage of cells in S phase. Results shown are mean + SD, with n = 4 replicates in each group. Results are mean ± SD. *, p < 0.05. **, p < 0.001
Mentions: We examined whether colonic epithelial cells were resting or proliferating state. DNA synthesis was measured in colonic epithelial cells followed. The percentage of BrdU-labeled S-phase cells were determined by observing labeled cells undergoing of the S-phase of the cell cycle. Our data demonstrated that colonic epithelial cells in CAC models without DPE treatment were predominantly in S phase (45 %), in G0/G1 phase (28 %), and in G2/M (26 %). Induction of DPE treatment change the percentage of cells in S phase through not in a dose dependent manner. DPE of 125 mg/kg BW (S phase = 36 %), 250 mg/kg BW (S phase = 17 %) and 500 mg/kg BW (S phase = 30 %) (Fig. 5).Fig. 5

View Article: PubMed Central - PubMed

ABSTRACT

Background: Indonesian mistletoe grows on various trees. Mango Mistletoes (Dendrophthoe pentandra) is one type of mistletoe that grown on mango tree (.benalu mangga in bahasa Indonesia). Our study used mistletoe as a parasitic plant that has been used for traditional medicine. It has been known that Dendrophtoe pentandra extract (DPE) anti-inflammatory and anticancer. Furthermore, it is necessary to follow-up study in vivo to evaluate the response to treatment of new cancer therapeutic agents. This research aimed to determine the levels of IL-22, myeloperoxide (MPO), proliferation and wild-type p53 expression after the administration of DPE to murine models of CAC.

Methods: Mouse colitis associated colon cancer (CAC) was induced firstly by azoxymethane (AOM) and followed by administration of drinking water containing 5&nbsp;% dextran sodium sulfate (DSS) in a cycle protocol, each cycle consisted of seven days of 5&nbsp;% DSS in the drinking water and followed by seven days of regular water. This study consists of five treatment groups: I was treated water only (control), II was administrated by (DSS only, without DPE), (III-V) were administrated by DPE (125&nbsp;mg/kg BW, 250&nbsp;mg/kg BW and 500&nbsp;mg/kg BW) respectively. The administrated of DPE were started from the 8th weeks, were continued until 21&nbsp;weeks. At the end of 21&nbsp;weeks of the experiment, mice were sacrificed, colon tissue was removed, and then subjected to ELISA, flow cytometry, real-time PCR and histology examination.

Results: Administration of DPE 250&nbsp;mg/kgBW significantly reduce the levels of IL-22 and MPO compared with DSS only group (p&thinsp;&lt;&thinsp;0.001; p&thinsp;&lt;&thinsp;0.001). Colonic epithelial cells proliferation of group IV (DPE 250&nbsp;mg/kgBW) were significantly lower than III and V groups. There was no significant change in the S phase in mice were treated DPE 125&nbsp;mg/kg BW and 500&nbsp;mg/kg BW, while administration of DPE 250&nbsp;mg/kg BW was able to increase the percentage of cells in S phase. The expression of mRNA p53 was up regulated in mice received DPE 125&nbsp;mg/kg BW.

Conclusion: These findings indicate that the DPE could inhibit colonic epithelial cells proliferation through p53 pathway independently. This study also showed that DPE could be potential sources of new therapy.

No MeSH data available.