Endharti Agustina Tri, Wulandari Adisti, Listyana Anik, Norahmawati Eviana, Permana Sofy
Department of Parasitology, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
Master Program in Biomedical Science, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
BMC Complement Altern Med. 2016 Sep 26;16(1):374. doi: 10.1186/s12906-016-1345-0.
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.
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 8 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.
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.
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.
印度尼西亚槲寄生生长在各种树木上。芒果槲寄生(五蕊寄生)是生长在芒果树上的一种槲寄生(印度尼西亚语为“benalu mangga”)。我们的研究将槲寄生作为一种已用于传统医学的寄生植物。已知五蕊寄生提取物(DPE)具有抗炎和抗癌作用。此外,有必要进行体内后续研究以评估新型癌症治疗药物的治疗反应。本研究旨在确定给结肠炎相关结肠癌(CAC)小鼠模型施用DPE后白细胞介素-22(IL-22)、髓过氧化物(MPO)水平、增殖情况及野生型p53表达。
首先用氧化偶氮甲烷(AOM)诱导小鼠患结肠炎相关结肠癌(CAC),然后按循环方案给予含5%葡聚糖硫酸钠(DSS)的饮用水,每个循环包括7天饮用含5% DSS的水,随后7天饮用普通水。本研究分为五个治疗组:I组仅给予水(对照组),II组仅给予(DSS,无DPE),(III - V)组分别给予DPE(125 mg/kg体重、250 mg/kg体重和500 mg/kg体重)。DPE的给药从第8周开始,持续至21周。在实验的第21周结束时,处死小鼠,取出结肠组织,然后进行酶联免疫吸附测定(ELISA)、流式细胞术、实时聚合酶链反应(PCR)和组织学检查。
与仅给予DSS的组相比,给予250 mg/kg体重的DPE显著降低了IL - 22和MPO水平(p < 0.001;p < 0.001)。IV组(250 mg/kg体重的DPE)的结肠上皮细胞增殖明显低于III组和V组。给予125 mg/kg体重和500 mg/kg体重DPE的小鼠S期无显著变化,而给予250 mg/kg体重的DPE能够增加S期细胞百分比。给予125 mg/kg体重DPE的小鼠中mRNA p53的表达上调。
这些发现表明DPE可通过p53途径独立抑制结肠上皮细胞增殖。本研究还表明DPE可能是新疗法的潜在来源。