CANCER SCIENCE
·
2023
·
IF 5.7
Bo‐Wen Zuo,Wan‐Xin Yao,Meng‐Die Fang,Juan Ren,Ling‐Lan Tu,Run‐Jie Fan,Yan‐Mei Zhang
The Brother of Regulator of Imprinted Sites (BORIS, gene symbol CTCFL) has previously been shown to promote colorectal cancer cell proliferation, inhibit cancer cell apoptosis, and resist chemotherapy. However, it is unknown whether Boris plays a role in the progression of in situ colorectal cancer. Here Boris knockout (KO) mice were constructed. The function loss of the cloned Boris mutation that was retained in KO mice was verified by testing its activities in colorectal cell lines compared with the Boris wild‐type gene. Boris knockout reduced the incidence and severity of azoxymethane/dextran sulfate‐sodium (AOM/DSS)‐induced colon cancer. The importance of Boris is emphasized in the progression of in situ colorectal cancer. Boris knockout significantly promoted the phosphorylation of γH2AX and the DNA damage in colorectal cancer tissues and suppressed Wnt and MAPK pathways that are responsible for the callback of DNA damage repair. This indicates the strong inhibition of colorectal cancer in Boris KO mice. By considering that the DSS‐promoted inflammation contributes to tumorigenesis, Boris KO mice were also studied in DSS‐induced colitis. Our data showed that Boris knockout alleviated DSS‐induced colitis and that Boris knockdown inhibited the NF‐κB signaling pathway in RAW264.7 cells. Therefore Boris knockout eliminates colorectal cancer generation by inhibiting DNA damage repair in cancer cells and relieving inflammation in macrophages. Our findings demonstrate the importance of Boris in the development of in situ colorectal cancer and provide evidence for the feasibility of colorectal cancer therapy on Boris.
研究领域:
癌症生物学
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分子生物学
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免疫学
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遗传学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2015
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IF 4.321
Lei Li,Haicheng Guo,Chen Shao,Shuili Yu,Daqiang Yin,Naiyun Gao,Ning Lu
The presence of algal organic matter (AOM) and emerging organic contaminants in surface drinking water sources has received increasing attention recently. Nevertheless, interactions between these two harmful co-existing compounds in water sources have rarely been reported. This study investigated the influence of AOM, including intracellular organic matter (IOM) and extracellular organic matter (EOM), on the photo-degradation of Diuron, under UV and visible light (VL) irradiation. Kinetics analyses indicated that both the direct and indirect photolysis of Diuron followed a pseudo-first-order reaction ( R 2 > 0.98). Diuron was rapidly removed under UV irradiation accompanied by minor impacts from AOM. Under VL irradiation, the photo-excited phycocyanin in the IOM was capable of accelerating Diuron degradation, whereas the coexistence of other organic compounds in the IOM inhibited the reaction due to a screening effect, resulting in a slower overall rate of Diuron degradation. By comparison, EOM promoted the reactions when pH exceeded 5.0. The AOM-mediated generation of triplet DOM ( 3 DOM ∗ ) accounted for 82% and 64% of the Diuron removal in the presence of IOM and EOM, respectively. Spectral excitation–emission matrices produced by AOM in solutions demonstrated the primary mechanisms of the co-existing AOM on Diuron degradation.
研究领域:
环境科学
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水处理工程
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光化学
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DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2026
·
IF 5.1
Yinyue Wang,Ruyi Zhang,Yangjiao Xu,Hongtao Shi,Xueyao Hu,Nairong Yu,Yu-Qiang Zhao,Baomin Fan,Guangzhi Zeng
NCTD-01 shows anti-inflammatory and cytotoxic effects in vitro and in vivo. • NCTD-01 exhibits low in vivo toxicity and a high oral MTD. • NCTD-01 suppresses AOM/DSS-induced colorectal cancer safely in mice. • NCTD-01 limits inflammation-to-cancer transition via NF-κB and Treg regulation. Although cantharidin (CTD) exhibits significant clinical efficacy against various cancers, its clinical utility is severely hampered by profound systemic toxicity. Thus, structural modification of CTD to obtain analogues with potent anticancer activity and lower toxicity is essential for advancing CTD-based therapeutics. Building on our previous synthesis of a series of C-5 alkynyl-substituted CTD analogues with potent anti-inflammatory properties, this study investigates the anticancer potential of a new analogue NCTD-01 demonstrated a favorable safety profile in mice, with the maximum tolerated dose (MTD) for oral administration exceeding 1852 mg/kg. In addition to exhibiting potent in vitro and in vivo anti-inflammatory activities comparable to its analogues, NCTD-01 displayed cytotoxicity against colon cancer cell lines and exhibited therapeutic efficacy in an azoxymethane/dextran sulfate sodium-induced orthotopic mouse model of colorectal cancer. Molecular analyses revealed that NCTD-01 reduced Ki-67 expression, suppressed the mRNA levels of pro-inflammatory and immunosuppressive mediators ( IL-1β , COX-2 , IL-6 , IL-10 , and TGF-β ) in colonic tumor tissues, and decreased serum levels of TNF-α and IL-1β. Furthermore, NCTD-01 treatment led to reduced expression of Foxp3, CD25, PD-1, and PD-L1, alongside enhanced CD8 and GITR expression in colorectal tissues, suggesting an effective modulation of tumor-associated immune responses. This study suggests that NCTD-01, a new C-5 alkynyl-substituted CTD analogue, may help alleviate the inflammation-to-cancer transition through tumor-associated immune modulation while maintaining a favorable safety profile, pointing to its potential as a candidate for anticancer drug discovery. Download: Download high-res image (99KB) Download: Download full-size image
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DOI
高影响因子
Oncology Letters
·
2021
·Vol. 21
·期 3
·1-1
·
IF 2.967
Jiaxue Hao,Xufen Dai,Juan Gao,Yuexuan Li,Zhaoling Hou,Zhongman Chang,Yuxin Wang
Colorectal cancer (CRC) is the third most common cancer worldwide, with high incidence and mortality rates. Conventional therapies, including surgery, chemotherapy and radiation, are extensively used for the treatment of CRC. However, patients present with adverse effects, such as toxicity, hepatic injury and drug resistance. Thus, there is an urgent requirement to identify effective and safe therapy for CRC. Curcumin (CUR), a polyphenol substrate extracted from the rhizome of Curcuma longa, has been extensively studied for the treatment of CRC due to its high efficacy and fewer side effects. Previous studies have reported that several signaling pathways, such as NF‑κB, Wnt/β‑catenin, are involved in the antitumor effects of CUR in vitro. However, the effect and mechanisms in vivo are not yet fully understood. The present study aimed to determine the molecular mechanism of colorectal cancer in vivo. Reverse transcription‑quantitative PCR, western blot and immunohistochemistry analyses were performed to determine the underlying molecular mechanism of curcumin's anti‑cancer effect in azoxymethane‑dextran sodium sulfate induced colorectal cancer. The results of the present study demonstrated that CUR suppressed tumorigenesis in AOM‑DSS induced CRC in mice, and anticancer effects were exerted by suppressing the expression of pro‑inflammatory cytokines, and downregulating Axin2 in the Wnt/β‑catenin signaling pathway. Taken together, these results exhibit the potential in vivo mechanisms of the anticancer effects of CUR, and highlight Axin2 as a potential therapeutic target for CRC.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2024
·Vol. 17
·期 3
·1523-1535
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IF 4.4
Wang Minyu,Gao Chongzheng,Lessing Duncan James,Chu Weihua
Colorectal cancer is the third most common cancer in the world today, and studies have shown that the ratio of Candida to Saccharomyces cerevisiae increased, and the abundance of S. cerevisiae in the intestines of patients with colorectal cancer decreased, which suggests that there is an imbalance in the proportion of fungi in the intestines of patients with colorectal cancer. The objective of this study was to screen S. cerevisiae isolate from traditional Chinese fermentation starters and assess its ability to ameliorate dysbiosis and to alleviate the carcinogenic process of azoxymethane/dextran sodium sulfate–induced colorectal cancer in mice model. S. cerevisiae strain SC-2201 was isolated and exhibited probiotic properties, including the ability to survive in an acidic pH environment and in the presence of bile salts in the gastrointestinal tract, as well as antioxidant activities. Oral administration of S. cerevisiae SC-2201 not only alleviated weight loss but also reduced colonic shortening and histological damage in azoxymethane/dextran sodium sulfate–induced colorectal cancer in mice. Furthermore, the administration of S. cerevisiae SC-2201 suppressed the expression of proinflammatory mediators, such as interleukin-1β, interleukin-6, cyclooxygenase-2, vascular endothelial growth factor, nucleotide-binding domain, leucine-rich repeat, and pyrin domain–containing protein 3. Specifically, the analysis of gut bacteriome showed a significant decrease in Bacteroidota and Campylobacterota levels, as well as an increase in Proteobacteria level in the colorectal cancer group, which was alleviated by supplementation with S. cerevisiae SC-2201. The analysis of the mycobiome revealed a significant increase in the levels of Basidiomycota , Apiosordaria , Naganishia , and Taphrina genera in the colorectal cancer group, which were alleviated after supplementation with S. cerevisiae SC-2201. However, the levels of Xenoramularia , Entoloma , and Keissleriella were significantly increased after administration with S. cerevisiae SC-2201. Overall, the findings of this study demonstrate that S. cerevisiae SC-2201 possesses potential probiotic properties and can effectively attenuate the development of colorectal cancer, highlighting its cancer-preventive potential. This is the first report of a S. cerevisiae strain isolated from traditional Chinese fermentation starters which showed good probiotic properties, and mitigated azoxymethane/dextran sodium sulfate–induced colorectal cancer by modulating the gut microbiome and blocking proinflammatory mediators in mice.
研究领域:
微生物学
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肿瘤学
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免疫学
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胃肠病学
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分子生物学
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药理学
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DOI
高影响因子
Food & Function
·
2020
·Vol. 11
·期 11
·9634-9650
·
IF 4.171
Jie Shen,Pei Li,Shuangshuang Liu,Qing Liu,Yue Li,Zheng Zhang,Chengmin Yang,Mengying Hu,Yuhua Sun,Chunnian He,Peigen Xiao
Despite that colorectal cancer (CRC) is a severe global health problem, effective chemopreventive strategies against CRC are still lacking. Huang-qin tea (HQT), a healthy herbal tea, is prepared from the aerial parts of Scutellaria baicalensis Georgi and has been consumed in China for thousands of years. HQT contains abundant flavonoids, which display potent anticancer effects, but no research studies have investigated the cancer-preventive effects of HQT on CRC in vivo. Here, we found that HQT inhibits azoxymethane-induced aberrant crypt foci (ACF) formation in a preneoplastic colonic ACF rat model. The essential role of the gut microbiota in the chemopreventive effect of HQT on CRC in a pseudo-germ-free rat model was confirmed. Besides, HQT modulates inflammatory cytokine expression by significantly decreasing IL-1β, IL-6, IL-10, and TNF-α expression, and elevating IFN-γ production. 16S rDNA sequencing analysis indicated that HQT regulated the gut microbiota by increasing the abundance of beneficial bacteria (Lachnoclostridium, Alistipes, Roseburia, and Lactococcus) and reducing the levels of Bacteroides, Parasutterella, and unidentified_Clostridiales. Fecal metabolomics showed that HQT modulated the AOM-induced metabolomic disorder, and these altered metabolites were almost involved in the lipid metabolic pathways. The Spearman correlation analysis revealed a correlation between the gut microbiota and fecal metabolites. Collectively, these results suggested that HQT exerted beneficial effects on host health by inhibiting inflammation, and by regulating the gut microbiota profile and certain metabolic pathways. In conclusion, HQT inhibits AOM-induced ACF formation by modulating the gut microbiota composition and improving metabolomic disorders, indicating the potential of HQT as a functional beverage candidate for the prevention and treatment of CRC.
研究领域:
肿瘤学
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药理学
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微生物学
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代谢组学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Yutong Ma,Jiaxi Li,Shuyu Liu,Wenlong Yu,Yaxin Sang,Xianghong Wang
Sulforaphane (SFN), a bioactive compound derived from cruciferous vegetables, exhibits chemopreventive properties agains various malignancies. Colitis-associated colorectal cancer (CAC) is a malignancy that develops through chronic inflammation-driven carcinogenesis in patients with long-standing inflammatory bowel disease. This study demonstrates a novel mechanism by which SFN protects against CAC through the simultaneous regulation of the Wnt/β-catenin signaling pathway and gut microbiota. Using an azoxymethane(AOM)/dextran sulfate salt sodium(DSS)-induced CAC mouse model to systematically evaluate SFN's therapeutic potential. Comprehensive assessments included histopathological examination, molecular analysis of inflammatory cytokines and proliferation markers, 16S rDNA sequencing for gut microbiota characterization, short-chain fatty acid (SCFA) profiling, and mechanistic investigation of Wnt/β-catenin pathway components. The experimental results showed that SFN intervention significantly alleviated clinical symptoms in mice, reduced inflammatory cytokine levels (IFN-γ, interferon-gamma; IHC, immune histochemical; IL-17, interleukin-17; IL-6, interleukin-6; MPO, myeloperoxidase) and suppressed proliferation markers (PCNA, proliferating cell nuclear antigen, antigen identified by monoclonal antibody Ki-67, Ki-67). Notably, SFN administration significantly restored the levels of major SCFAs, including acetate, propionate, and butyrate, which were markedly reduced in CAC mice. Mechanistically, SFN inhibited the Wnt/β-catenin signaling pathway by down-regulating the expression of β-catenin, cyclin D1 and c-myc expression. Concurrently, SFN restored gut microbial diversity, increased beneficial bacteria, and reduced pathogenic genera. The observed increase in SCFAs levels was correlated with these microbial improvements, and orrelation analysis further linked these microbial shifts to clinical improvements. Our findings reveal that SFN mitigates CAC progression by coordinated modulation of both Wnt/β-catenin signaling and gut microbiota, with the restoration of SCFAs production representing a key functional outcome, highlighting its potential as a multi-target dietary intervention for colorectal cancer prevention.
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产品关联
DOI
高影响因子
Gut Microbes
·
2025
·
IF 11
Yong Sun,Qiwen Wang,Yao Jiang,Jiamin He,Dingjiacheng Jia,Man Luo,Wentao Shen,Qingyi Wang,Yadong Qi,Yifeng Lin,Ying Zhang,Lan Wang,Liangjing Wang,Shujie Chen,Lina Fan
Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the ApcMin/+ spontaneous adenoma model. Our investigation revealed that L. intestinalis increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by L. intestinalis recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between L. intestinalis, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.
研究领域:
肿瘤学
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微生物学
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免疫学
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DOI
PubMed
高影响因子
Nutrients
·
2026
·Vol. 18
·期 2
·310
·
IF 5
Xin Zhang,Di Wang,Yang Wang,Meimei Wang,Juncheng Wang,Yue Sun,Siman Chen,Xinting Qu,Antong Xia,Hongxin Liu,Jihui Wang,Meng Liu
(E)-Flavokawain A (FKA), the primary chalcone constituent of Piper methysticum , exhibits diverse pharmacological properties and holds significant potential for therapeutic development. Objectives : This study aims to investigate the anti-colorectal cancer effects and mechanisms of FKA. Methods : Using AOM/DSS-induced colorectal cancer models in C57 mice, the research examines the impact of different FKA doses, employing 16S rRNA and metabolomics to explore the potential mechanism. Results : The findings indicated that FKA significantly inhibited the progression of colorectal cancer in C57 mice by modulating the composition of the gut microbiota. This modulation involved the suppression of endotoxin secretion by pathogenic bacteria and the concurrent augmentation of beneficial bacteria. Furthermore, in the context of metabolic pathways, FKA regulates lipid metabolism and arachidonic acid metabolism, thereby mitigating the inflammatory transformation associated with colorectal cancer. Conclusions : These findings provide valuable insights supporting the potential of FKA as a viable preventive strategy against CRC.
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 9
·8259-8272
·
IF 4.171
Shuhua Shan,Yue Xie,Chengying Zhang,Bin Jia,Hanqing Li,Zhuoyu Li
Homology of medicine and food-zizyphi spinosi semen (ZSS) exhibits abundant pharmacological activities, such as sedation, hypnosis and anti-depression. In the present study, the water soluble polyphenols extracted from ZSS via the acid digestion method were named ZSSP, and exhibited significant anti-colorectal cancer (CRC) activity, characterized by restraining cell proliferation, promoting cell apoptosis and increasing chemo-sensitivity of CRC cells. The potential of ZSSP in vivo was further evaluated in an AOM/DSS-induced colitis-associated carcinogenesis (CAC) mouse model. Intriguingly, ZSSP diminished the number and volume of CAC polyps in mice in a dose-dependent manner, and effectively limited the damage of mice organs induced by AOM/DSS. The immunohistochemistry result showed that the elevated CRC early markers in CAC mice, such as COX-II, EMR1, and Ki67, were potently prevented by the ZSSP treatment. Further, the component in ZSSP with the anti-CRC activity was identified as spinosin by the macroporous resin of SP207 and RP-HPLC-MS/MS. Interestingly, during the extraction process, sodium ions were introduced forming spinosin·Na+, which had better water solubility and more remarkable anti-CRC activity than the spinosin. This study provides a new pharmacological property of spinosin derived from ZSS, inhibiting the growth of human CRC cells and colitis-associated CRC in mice, which indicates its potential use as a natural agent against CRC.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Jingya Ruan,Huimin Li,Mengqi Lu,Mimi Hao,Fan Sun,Haiyang Yu,Yi Zhang,Tao Wang
Background Jujube, a popular fruit from the Rhamnaceae family, relieves colorectal inflammation caused by spleen deficiency and has been used in many formulas in clinical for decades to treat colorectal cancer (CRC). As of yet, the therapeutic substances and mechanism of their action are unknown. Purpose The purpose of this study is to define the therapeutic substances of jujube and its mechanism of action in treating CRC . Methods The pharmacological effects of jujube extract and its fractions were evaluated in vivo using a CRC mouse model induced by AOM/DSS. The DAI value, colon length, mortality, tumor burden, and histological tumor size of the treated animals were compared. To explore the potential therapeutic substances, LC-MS analysis was conducted to characterize the serum migration components. A network pharmacology experiment was carried out for potential molecular targets. To verify the therapeutic substances as well as the molecular mechanism of jujube intervening CRC, cellular MTT assay of the serum migration components, Western blot and IHC tests were conducted. Results The in vivo pharmacological studies showed that compared to AOM/DSS treated mice, the mortality and DAI value, tumor burden, and histological tumor size of jujube extract and its fat-soluble fraction (mainly contained triterpenes) treated mice were significantly reduced, and their colon lengths were obviously longer than AOM/DSS treated mice. The targeted-LC/MS analysis supposed triterpenes 3, 7, 9, 11, 12, 14, 17 – 21, and 25 – 28 to be the serum migration components, which might be the potential therapeutic substances. In the network pharmacology experiment, the GO annotation and enrichment analysis of the KEGG pathway indicated that PI3K-Akt pathway and inflammatory reaction were important factors for jujube inhibiting CRC. Cellular MTT assay of serum migration components indicated that the potential effective substances from fat-soluble fraction to be triterpenes 3, 7, 17, 19, 20, and 25. The Western blot and IHC assays implied that the jujube extract, its fat-soluble fraction, and triterpenes 7, 17, and 20 showed inhibition on the expression of PI3K/Akt/NF-κB signaling pathway-related proteins. Additionally, it was noted in the pharmacodynamic experiment that ZJL's effectiveness was more apparent than ZJH and SQL in tumor burden rate, colon length, and spleen weight, which indicated that the efficacy of ZJ is contributed from CD and SQ, and they may have a synergistic effect on anti-CRC. Conclusion These results for the first time provide evidence that jujube triterpenes possess an anti-CRC effect, their mechanism was involving the control of the PI3K/Akt/NF-κB signaling pathway. What's more, the potential synergistic effect of the fat-soluble and water-soluble components found in this study provided a solid foundation for our deep understanding of how jujube can ameliorate CRC.
研究领域:
药理学
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肿瘤学
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分子生物学
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中医药
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Li-Ying Han,Hao Yu,Shuai Wang,Yong-Rui Bao,Tian-Jiao Li,Ying Zheng,Xi Luo,Meng-Nan Jia,Qiang Zhang,Xian-Sheng Meng
Ethnopharmacological relevance Colorectal cancer (CRC) belongs to the category of intestinal wind, anal ulcer, abdominal mass and other diseases in traditional Chinese medicine (TCM). Floris Sophorae Powder (F.S), is a classical prescription is recorded in Puji Benshi Fang for the treatment of intestinal carbuncle. It has been incorporated into the prescriptions for the treatment of intestinal diseases and achieved remarkable results in modern medicine. However, the mechanism of F.S in the treatment of colorectal cancer remains unclear and requires further study. Aim of the study To investigate F.S in treating CRC and clarify the underlying mechanism. Materials and methods This study was based on Dextran Sulfate Sodium Salt (DSS) combined with Azoxymethane (AOM) induced CRC mouse model to clarify the pharmacological effects of F.S. The serum metabolomics was used to study the mechanism of action, and the chemical composition of F.S was found by UPLC-Q-TOF-MS. The rationality of serm metabolomics results was verified through the clinical target database of network pharmacology, and the upstream and downstream targets of related pathways were found. The mechanism pathway was verified by Western blot to clarify its mechanism of action. Results In vivo pharmacological experiments showed that F.S inhibited tumor growth and improved hematochezia. The vital signs of mice in the high-dose F.S group approached to those in the control group. A total of 43 differential metabolites were found to be significantly changed by serum metabolomics. F.S could modulate and recover most of the differential metabolites, which proved to be closely related to the KRAS/MEK-ERK signaling pathway. A total of 46 compounds in F.S were identified, and the rationality of serm metabolic pathway was verified by network pharmacology. Western blot results also verified that the expression of KRAS, E2F1, p-MEK and p-ERK were significantly decreased after F.S treatment. Conclusion Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.
研究领域:
药理学
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肿瘤学
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中医
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代谢组学
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信号转导
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）