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 γ-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.
Highlights
Colorectal cancer (CRC) is the third most common cancer globally
As described by Tanaka et al [7], the Azoxymethane/Dextran sodium sulphate (AOM/dextran sodium sulphate (DSS)) model completely reproduced the multi-step process of carcinogenesis characterized by the canonical phases of initiation, promotion, and progression.Different preclinical studies support the use of the AOM/DSS model as aninflammation/oxidative stress-related carcinogenic model to perform the intervention studies of synthetic agents or natural plant compounds
This study demonstrated that Angelica sinensis root (ASR) extract administration either in the initial or promotion stages of theTAhiOs Mstu/DdySSdemmoodnesltrreadteudcethdaatmAoSuRnetxstorafc8t-aodxmogiuniasntrinateioanndeitγh-eHr2inAtXheinintuitmialoorsr,pwrohmicohtionndisctatgeeds tohfatthceelAlsOwMe/rDe SpSromteocdteedl rferodmucDedNaAmdoaumntasgoef. 8H-oxwoegvuearn, tinhesaenaddγm-iHn2isAtrXatinontus mledortso, wophpicohsiitnedeifcfaetcetds othnactacreclilns owgeerneepsirsotehcrtoeudgfhroPm53D-mNeAdidaatemdagape.oHptoowsiesv. eTrh, ethsesreeasudlmtsininisfterrattihoantstlheed ctoanocpepr-opsrietevenffteicvtes eofnfectarocfinAoSgReneexstirsactht rwouasghstaPg5e3-dmeepdeinadteednta, paosptthoesiasn. tTiohxeisdearnetssuultpspilnefmerentht aetxethrteedcasnpcecri-fpicrervoelnestivaet deifffeecrteonft sAtaSgResexotfracactrcwinaosgsetnaegsei-sd. ependent, as the antioxidant supplement exerted specific roles at
Summary
Colorectal cancer (CRC) is the third most common cancer globally. only about 20% of CRC cases have been associated with heritable genetic changes, and the largest fraction has been linked to environmental factors. As described by Tanaka et al [7], the AOM/DSS model completely reproduced the multi-step process of carcinogenesis characterized by the canonical phases of initiation, promotion, and progression.Different preclinical studies support the use of the AOM/DSS model as aninflammation/oxidative stress-related carcinogenic model to perform the intervention studies of synthetic agents or natural plant compounds. For these reasons, the AOM/DSS model was chosen for our study to evaluate the effect of Angelica sinensis root (ASR) extract on cancer prevention
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