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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

The experiment design of mice was induced Colitis Associated Colon Cancer (CAC) and DPE administration. Mouse was induced firstly by azoxymethane (AOM) and followed by administration of drinking water containing 5 % dextran sodium sulfate (DSS) in a cycle protocol for 7 days at weeks (1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) and followed by seven days of regular water at weeks (2, 4, 6, 8, 10, 12, 14, 16, 18 and 20). For the experiment, mice were divided into 5 groups; I received water (control); II was given DSS only; III-V groups were treated 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 until 21th weeks. At the end of 21 weeks, mice in all groups were sacrificed ○ = PBS, ● = AO, ↓= DSS, ▲ = water (H2O), ↕ = DPE
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Fig1: The experiment design of mice was induced Colitis Associated Colon Cancer (CAC) and DPE administration. Mouse was induced firstly by azoxymethane (AOM) and followed by administration of drinking water containing 5 % dextran sodium sulfate (DSS) in a cycle protocol for 7 days at weeks (1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) and followed by seven days of regular water at weeks (2, 4, 6, 8, 10, 12, 14, 16, 18 and 20). For the experiment, mice were divided into 5 groups; I received water (control); II was given DSS only; III-V groups were treated 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 until 21th weeks. At the end of 21 weeks, mice in all groups were sacrificed ○ = PBS, ● = AO, ↓= DSS, ▲ = water (H2O), ↕ = DPE

Mentions: Mice were given a single i.p. injection of 10 mg/kg azoxymethane (AOM; (Sigma-Aldrich, USA, Cat A5486) or vehicle (PBS) on experimental day 1. At one week post injection, colitis was induced by providing drinking water containing 5 % DSS (ICN Biomedical Inc, CA, USA) for a week. DSS was administered in a cycle protocol, each cycle consisting of 7 days of 5 % DSS and followed by one week of regular water. Colon cancer was induced by cyclical DSS treatment, which consisted of 1 week of 5 % DSS followed by 7 days of untreated water (Fig. 1). The oral administration of DPE starting at 8 weeks was continued until 21 weeks [21]. Mice were randomly divided into five groups (Fig. 1). Control group received water (vehicle). Group ll was given 5 % DSS only. Group (lll-V) were received DPE at 125, 250 or 500 mg/kg body weight, respectively. The dose of DPE 125 mg/kg-500 mg/kg were used previously [21]. Colon tissue was removed and cleaned, then subjected to ELISA, flowcytometry, qPCR and immunohistochemistry.Fig. 1


Dendrophthoe pentandra (L.) Miq extract effectively inhibits inflammation, proliferation and induces p53 expression on colitis-associated colon cancer
The experiment design of mice was induced Colitis Associated Colon Cancer (CAC) and DPE administration. Mouse was induced firstly by azoxymethane (AOM) and followed by administration of drinking water containing 5 % dextran sodium sulfate (DSS) in a cycle protocol for 7 days at weeks (1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) and followed by seven days of regular water at weeks (2, 4, 6, 8, 10, 12, 14, 16, 18 and 20). For the experiment, mice were divided into 5 groups; I received water (control); II was given DSS only; III-V groups were treated 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 until 21th weeks. At the end of 21 weeks, mice in all groups were sacrificed ○ = PBS, ● = AO, ↓= DSS, ▲ = water (H2O), ↕ = DPE
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5037598&req=5

Fig1: The experiment design of mice was induced Colitis Associated Colon Cancer (CAC) and DPE administration. Mouse was induced firstly by azoxymethane (AOM) and followed by administration of drinking water containing 5 % dextran sodium sulfate (DSS) in a cycle protocol for 7 days at weeks (1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) and followed by seven days of regular water at weeks (2, 4, 6, 8, 10, 12, 14, 16, 18 and 20). For the experiment, mice were divided into 5 groups; I received water (control); II was given DSS only; III-V groups were treated 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 until 21th weeks. At the end of 21 weeks, mice in all groups were sacrificed ○ = PBS, ● = AO, ↓= DSS, ▲ = water (H2O), ↕ = DPE
Mentions: Mice were given a single i.p. injection of 10 mg/kg azoxymethane (AOM; (Sigma-Aldrich, USA, Cat A5486) or vehicle (PBS) on experimental day 1. At one week post injection, colitis was induced by providing drinking water containing 5 % DSS (ICN Biomedical Inc, CA, USA) for a week. DSS was administered in a cycle protocol, each cycle consisting of 7 days of 5 % DSS and followed by one week of regular water. Colon cancer was induced by cyclical DSS treatment, which consisted of 1 week of 5 % DSS followed by 7 days of untreated water (Fig. 1). The oral administration of DPE starting at 8 weeks was continued until 21 weeks [21]. Mice were randomly divided into five groups (Fig. 1). Control group received water (vehicle). Group ll was given 5 % DSS only. Group (lll-V) were received DPE at 125, 250 or 500 mg/kg body weight, respectively. The dose of DPE 125 mg/kg-500 mg/kg were used previously [21]. Colon tissue was removed and cleaned, then subjected to ELISA, flowcytometry, qPCR and immunohistochemistry.Fig. 1

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