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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.


Related in: MedlinePlus

Colonic proliferation cells from the colon CAC mice models. The cell proliferation patterns in the colon tissue were assessed by using BrdU immunohistochemistry. Epithelial proliferation enhanced in colon of CAC mice model. Colon tissues were treated with anti BrDu antibody counterstained with hematoxylin and visualized under the light microscope. Cell proliferation identified by BrdU immunohistochemical staining of paraffin section. Brown-color nucleus indicates BrdU-positive cells. (A) Control group received water, (B) Group was administrated DSS 5 % only, (C), (D) and (E) mice were administrated DPE orally 125, 250 and 500 mg/kg, respectively. Red arrow: the BrdU positive cell. All images were magnified at 400x and representative four independent experiments with consistent results. (F). Number of BrdU positive cells. 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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Fig4: Colonic proliferation cells from the colon CAC mice models. The cell proliferation patterns in the colon tissue were assessed by using BrdU immunohistochemistry. Epithelial proliferation enhanced in colon of CAC mice model. Colon tissues were treated with anti BrDu antibody counterstained with hematoxylin and visualized under the light microscope. Cell proliferation identified by BrdU immunohistochemical staining of paraffin section. Brown-color nucleus indicates BrdU-positive cells. (A) Control group received water, (B) Group was administrated DSS 5 % only, (C), (D) and (E) mice were administrated DPE orally 125, 250 and 500 mg/kg, respectively. Red arrow: the BrdU positive cell. All images were magnified at 400x and representative four independent experiments with consistent results. (F). Number of BrdU positive cells. Results shown are mean + SD, with n = 4 replicates in each group. Results are mean ± SD. *, p < 0.05. **, p < 0.001

Mentions: This study, epithelial cells proliferation was observed by using anti-BrdU staining performed by Immunohistochemistry. The microscopic appearance of colonic epithelial cells of CAC mice model showed undergo proliferation in DSS only group. Colonic epithelial cells proliferation was significantly higher in DSS-induced CAC models than DPE treatment groups (p = 0.02) (Fig. 4). Administration of DPE could decreased proliferation of epithelial cells. In this study, DPE suppressed carsinogenesis by reducing the proliferation of epithelial cells.Fig. 4


Dendrophthoe pentandra (L.) Miq extract effectively inhibits inflammation, proliferation and induces p53 expression on colitis-associated colon cancer
Colonic proliferation cells from the colon CAC mice models. The cell proliferation patterns in the colon tissue were assessed by using BrdU immunohistochemistry. Epithelial proliferation enhanced in colon of CAC mice model. Colon tissues were treated with anti BrDu antibody counterstained with hematoxylin and visualized under the light microscope. Cell proliferation identified by BrdU immunohistochemical staining of paraffin section. Brown-color nucleus indicates BrdU-positive cells. (A) Control group received water, (B) Group was administrated DSS 5 % only, (C), (D) and (E) mice were administrated DPE orally 125, 250 and 500 mg/kg, respectively. Red arrow: the BrdU positive cell. All images were magnified at 400x and representative four independent experiments with consistent results. (F). Number of BrdU positive cells. Results shown are mean + SD, with n = 4 replicates in each group. Results are mean ± SD. *, p < 0.05. **, p < 0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5037598&req=5

Fig4: Colonic proliferation cells from the colon CAC mice models. The cell proliferation patterns in the colon tissue were assessed by using BrdU immunohistochemistry. Epithelial proliferation enhanced in colon of CAC mice model. Colon tissues were treated with anti BrDu antibody counterstained with hematoxylin and visualized under the light microscope. Cell proliferation identified by BrdU immunohistochemical staining of paraffin section. Brown-color nucleus indicates BrdU-positive cells. (A) Control group received water, (B) Group was administrated DSS 5 % only, (C), (D) and (E) mice were administrated DPE orally 125, 250 and 500 mg/kg, respectively. Red arrow: the BrdU positive cell. All images were magnified at 400x and representative four independent experiments with consistent results. (F). Number of BrdU positive cells. Results shown are mean + SD, with n = 4 replicates in each group. Results are mean ± SD. *, p < 0.05. **, p < 0.001
Mentions: This study, epithelial cells proliferation was observed by using anti-BrdU staining performed by Immunohistochemistry. The microscopic appearance of colonic epithelial cells of CAC mice model showed undergo proliferation in DSS only group. Colonic epithelial cells proliferation was significantly higher in DSS-induced CAC models than DPE treatment groups (p = 0.02) (Fig. 4). Administration of DPE could decreased proliferation of epithelial cells. In this study, DPE suppressed carsinogenesis by reducing the proliferation of epithelial cells.Fig. 4

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.


Related in: MedlinePlus