Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancer
This study aimed to evaluate the preventive efficacy of tocotrienol in inhibiting the nuclear factor-kappa B (NF-κB) mediated inflammation pathways in colorectal cancer. We utilized the azoxymethane (AOM) and dextran sulfate sodium salt (DSS) to induce colitis-associated colorectal cancer (CAC) mice...
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Elsevier
2024-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X24000495 |
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| author | Qian Li Shujing Zhang Qinghong Zhou Chenxi Gu Yinghua Liu Jing Zhang Jingshu Zhang |
| author_facet | Qian Li Shujing Zhang Qinghong Zhou Chenxi Gu Yinghua Liu Jing Zhang Jingshu Zhang |
| author_sort | Qian Li |
| collection | DOAJ |
| description | This study aimed to evaluate the preventive efficacy of tocotrienol in inhibiting the nuclear factor-kappa B (NF-κB) mediated inflammation pathways in colorectal cancer. We utilized the azoxymethane (AOM) and dextran sulfate sodium salt (DSS) to induce colitis-associated colorectal cancer (CAC) mice model. In generating a CAC model, mice were intraperitoneally injected with AOM at a concentration of 10 mg/kg body weight. Seven days after the AOM injection, mice drinking water containing 3 % DSS for 1 week, followed by a 2-week period of regular water. This cycle of DSS treatment (1-week 3 % DSS+2-week water) was repeated for two additional cycles. Mice were randomly divided into five groups (n = 20/group), including Blank group, Model group, three different dosages tocotrienol groups (Low dose group [50 mg/kg], Medium dose group [75 mg/kg], and High dose group [100 mg/kg]). The protective effects of tocotrienol were assessed using histological, flow cytometry, western blot and mouse Luminex assay. Compared with the blank group, expressions of toll-like receptor 4 (TLR4), myeloid differentiation protein 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6), NF-κB, Interleukin (IL)-6 and tumor necrosis factor (TNF) −α were increased in model group, while IL-4 and IL-10 were decreased in model group (P<0.05). Tocotrienol prevented carcinogenesis and decreased the IL-6, TNF-α, MyD88, TLR4, TRAF-6 and NF-κB expression levels, compared with the model group (P<0.05). Compared with the model group, the expression of IL-10 was increased in medium dose group and high dose group (P<0.05). The protective effects of tocotrienol may be related to the inhibition of TLR4 /MyD88 /NF-κB mediated inflammatory signaling pathways. Therefore, the use of tocotrienol can improve the abnormal expression of cytokines in a mouse model of colorectal cancer and inhibit the occurrence and development of colorectal cancer. |
| format | Article |
| id | doaj-art-c68e65ef6901417ebb10480de948edac |
| institution | DOAJ |
| issn | 2666-027X |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Toxicology |
| spelling | doaj-art-c68e65ef6901417ebb10480de948edac2025-08-20T02:39:18ZengElsevierCurrent Research in Toxicology2666-027X2024-01-01710019610.1016/j.crtox.2024.100196Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancerQian Li0Shujing Zhang1Qinghong Zhou2Chenxi Gu3Yinghua Liu4Jing Zhang5Jingshu Zhang6School of Public Health, Qilu Medical University, Shandong 255300, ChinaDepartment of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China; NHC Specialty Laboratory of Food Safety Risk Assessment and Standard Development, Tianjin 300011, ChinaDepartment of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China; NHC Specialty Laboratory of Food Safety Risk Assessment and Standard Development, Tianjin 300011, ChinaDisease Prevention and Control Center of Binhu District, Wuxi City, Jiangsu 214100, ChinaDepartment of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China; NHC Specialty Laboratory of Food Safety Risk Assessment and Standard Development, Tianjin 300011, ChinaDepartment of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China; NHC Specialty Laboratory of Food Safety Risk Assessment and Standard Development, Tianjin 300011, ChinaSchool of Public Health, Nanjing Medical University, Nanjing 211166, China; Corresponding author at: Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.This study aimed to evaluate the preventive efficacy of tocotrienol in inhibiting the nuclear factor-kappa B (NF-κB) mediated inflammation pathways in colorectal cancer. We utilized the azoxymethane (AOM) and dextran sulfate sodium salt (DSS) to induce colitis-associated colorectal cancer (CAC) mice model. In generating a CAC model, mice were intraperitoneally injected with AOM at a concentration of 10 mg/kg body weight. Seven days after the AOM injection, mice drinking water containing 3 % DSS for 1 week, followed by a 2-week period of regular water. This cycle of DSS treatment (1-week 3 % DSS+2-week water) was repeated for two additional cycles. Mice were randomly divided into five groups (n = 20/group), including Blank group, Model group, three different dosages tocotrienol groups (Low dose group [50 mg/kg], Medium dose group [75 mg/kg], and High dose group [100 mg/kg]). The protective effects of tocotrienol were assessed using histological, flow cytometry, western blot and mouse Luminex assay. Compared with the blank group, expressions of toll-like receptor 4 (TLR4), myeloid differentiation protein 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6), NF-κB, Interleukin (IL)-6 and tumor necrosis factor (TNF) −α were increased in model group, while IL-4 and IL-10 were decreased in model group (P<0.05). Tocotrienol prevented carcinogenesis and decreased the IL-6, TNF-α, MyD88, TLR4, TRAF-6 and NF-κB expression levels, compared with the model group (P<0.05). Compared with the model group, the expression of IL-10 was increased in medium dose group and high dose group (P<0.05). The protective effects of tocotrienol may be related to the inhibition of TLR4 /MyD88 /NF-κB mediated inflammatory signaling pathways. Therefore, the use of tocotrienol can improve the abnormal expression of cytokines in a mouse model of colorectal cancer and inhibit the occurrence and development of colorectal cancer.http://www.sciencedirect.com/science/article/pii/S2666027X24000495Annatto-tocotrienolColorectal cancerTLR4 signalingCytokines |
| spellingShingle | Qian Li Shujing Zhang Qinghong Zhou Chenxi Gu Yinghua Liu Jing Zhang Jingshu Zhang Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancer Current Research in Toxicology Annatto-tocotrienol Colorectal cancer TLR4 signaling Cytokines |
| title | Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancer |
| title_full | Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancer |
| title_fullStr | Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancer |
| title_full_unstemmed | Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancer |
| title_short | Tocotrienol suppresses colitis-associated cancer progression through TLR4 signaling in a mouse model of colorectal cancer |
| title_sort | tocotrienol suppresses colitis associated cancer progression through tlr4 signaling in a mouse model of colorectal cancer |
| topic | Annatto-tocotrienol Colorectal cancer TLR4 signaling Cytokines |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X24000495 |
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