Abstract

BackgroundIndonesian 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.MethodsMouse 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.ResultsAdministration 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.ConclusionThese 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.

Highlights

  • Dextran sulfate sodium induced colitis associated cancer (CAC) Based on previous studies, dextran sodium sulfate (DSS) was used in combination with AOM, received a chemical carcinogen which induces colorectal cancer in mice

  • Dendrophtoe pentandra extract (DPE) decreased the level of IL-22 in the colon of CAC models AOM and DSS administration increase IL-22 levels in supernatant colon culture significantly (p = 0.000)

  • The administration of DPE at all doses in group lll (doses (125 mg/kg), p = 0.000; group lV (250 mg /kg), p = 0.000, group V (500 mg/kg) p = 0.010) decreased the levels of IL-22 significantly compared with DPE (−) group (Fig. 2)

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Summary

Introduction

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. People in Indonesia usually called the mistletoe depend on the host plant where it grew, such as benalu mangga (mistletoe which used mango as host). Mistletoe is considers as an unwanted plant to economically important horticultural plant, in the other side, mistletoe is known as one of medicinal plant used in traditional/alternative medicine in Indonesia and other countries such as in treatment for cough, diabetes, hypertension, cancer, diuretic. Quercetin has anti-oxidant, anti-inflammatory, anti-cancer, and immune modulator effect [3,4,5]. Quercetin improve the action of the drug 5-Fluorouracil (5-FU) promoting increased expression of p53 and apoptosis in breast cancer T47D cells [6, 7]

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