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Effect of Angelica sinensis Root Extract on Cancer Prevention in Different Stages of an AOM/DSS Mouse Model.

ABSTRACT: Angelica sinensis root (ASR) extract was obtained to investigate its effects on colorectal carcinogenesis in different stages of an Azoxymethane/Dextran sodium sulphate (AOM/DSS) model. In this study, we showed that ASR extract administration in the initial stage of the AOM/DSS model had cancer preventive effects with decreasing tumor incidence and a high-grade of intraepithelial neoplasia incidence. With respect to DNA damage, the amounts of 8-oxoguanine and ?-H2AX were suppressed in colon tissue. The balance of apoptosis and proliferation was approaching the normal state. In contrast, ASR extract administration in the promotion stage of the AOM/DSS model accelerated the progression of carcinogenesis. The maximum tumor size reached 49.85 ± 25.04 mm³. High-grade pathological changes were significantly increased. Decreased DNA damage and P53 level reflected the disrupted reactive oxygen species (ROS) concentration in colorectal tissue, which led to an imbalance of proliferative and apoptotic relationships. These findings suggested that the cancer-preventive effect of ASR extract may be stage-dependent in the process of carcinogenesis.

SUBMITTER: Zhao B

PROVIDER: S-EPMC5578140 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Effect of Angelica sinensis Root Extract on Cancer Prevention in Different Stages of an AOM/DSS Mouse Model.

Zhao Bochen B Kang Qian Q Peng Yu Y Xie Yuanping Y Chen Cheng C Li Bingshao B Wu Qing Q

International journal of molecular sciences 20170811 8

<i>Angelica sinensis</i> root (ASR) extract was obtained to investigate its effects on colorectal carcinogenesis in different stages of an Azoxymethane/Dextran sodium sulphate (AOM/DSS) model. In this study, we showed that ASR extract administration in the initial stage of the AOM/DSS model had cancer preventive effects with decreasing tumor incidence and a high-grade of intraepithelial neoplasia incidence. With respect to DNA damage, the amounts of 8-oxoguanine and γ-H2AX were suppressed in col ...[more]

PMID: 28800083

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Project description:IntroductionAngiogenin-1 (Ang1) and angiogenin-4 (Ang4) are 14-kDa ribonucleases with potent angiogenic and antimicrobial properties. The role of Ang1 and Ang4 in chronic colitis and colitis-associated cancer has not been previously studied.MethodsWild-type (WT) and angiogenin-1 knock-out (Ang1-KO) C57BL/6 mice were given azoxymethane, a colon carcinogen, 2 days in advance of three cycles of 3.5% dextran sodium sulfate (DSS). Disease activity index (DAI) was recorded, a colonoscopy was performed after each DSS treatment, and mice were euthanized (colitis, recovery, cancer) with tissue evaluated by histopathology. Ang1, Ang4, TNF-α, Il-1F062, IL-6, IL-10, IL-23, IL-33 mRNA levels were analyzed by RT-PCR.ResultsAng1-KO mice exhibited more severe colitis compared to WT mice during both the acute (P<0.05) and recovery (P<0.05) phases of each DSS cycle. Consistent with these results, colonic TNF-α, IL1-β, IL-6, IL-10, and IL-33 mRNA levels were significantly upregulated in Ang1-KO mice (P<0.05). While Ang4 increased to similar levels in both WT and Ang1-KO mice during colitis and recovery phases, WT mice were distinguished by a significant upregulation of Ang1. Interestingly, despite the reduced colitis, WT mice developed significantly more tumors compared to Ang1-KO mice (P<0.05). 134 tumors formed in WT mice (4.6 tumors/mouse) while only 46 tumors formed (1.5 tumors/mice) in Ang1-KO mice, which were also characterized by a 34-fold decrease in Ang4 compared to WT mice and the complete absence of Ang1.ConclusionsIn a mouse model of colitis-associated cancer, Ang1-KO mice develop more severe colitis, but fewer tumors compared to WT mice. Ang1 levels correlate with the severity of colitis and the development of colitis-associated cancer, while Ang4 was upregulated during both colitis and cancer. Ang1 and Ang4 play important regulatory roles in the response to chronic colitis and the development of colitis-associated cancer and may serve as novel therapeutic targets.

Dataset Information

Effect of Angelica sinensis Root Extract on Cancer Prevention in Different Stages of an AOM/DSS Mouse Model.

Publications

Effect of Angelica sinensis Root Extract on Cancer Prevention in Different Stages of an AOM/DSS Mouse Model.

Similar Datasets

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