Anti-colorectal cancer activity of mannatide from spent brewer's yeast by regulating immune cells and immune function in the tumor microenvironment

• Published in: International journal of biological macromolecules Vol. 280; no. Pt 1; p. 135531
• Main Authors: Li, Fei, Sun, Xiaopeng, Gao, Xiang, Zhao, Shuang, Tavakoli, Samad, Du, Zubo, Wei, Yuxi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2024
• Subjects: Anti-colorectal cancer; Immunotherapy; Mannatide; M1; COX-2; M2; IHC; SPF; TNF; IFN; Arg-1; TAMs; ANOVA; FBS; Immunotherapy; iNOS; CCK-8; Anti-colorectal cancer; IL; MOD; DAB; H&E; DAPI; IgG-HRP; EDTA; TME; ZO-1; Mannatide; CRC; GRAS; RPMI; MTE; 5-FU; ELISA
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.135531

Chemotherapy and radiotherapy are generally accompanied by adverse effects, which reduce tolerance to cancer therapies. Immunonutrition improves the clinical outcomes of cancer patients. Hence, natural immunomodulator is therefore considered as a favorable alternative. This study aimed to elucidate the anti-colorectal cancer (CRC) effect of mannatide (MTE) from the immunostimulatory perspective. MTE (concentrations≥1200 μg/mL) significantly inhibited HT-29 cells viabilities compared with the 5-fluorouracil (5-FU) group and all predetermined concentrations of MTE promoted the proliferation of RAW264.7 (p < 0.01). Moreover, MTE treatment suppressed tumor growth, decreased leukocyte and platelet count, and regulated immune organ indexes compared with the model group. In comparison of Model and 5-FU groups, MTE treatment reshaped tumor-associated macrophages (TAMs) from alternatively activated macrophages (M2)-like into classical activated macrophages (M1)-like phenotype. Also, it increased the proportion of CD8+ and CD4+ T cells accompanied by secreting pro-inflammatory cytokines (interferon (IFN)-γ and tumor necrosis factor (TNF)-α) and decreasing pro-inflammatory cytokines (interleukin (IL)-4, interleukin (IL)-6, arginine (Arg)-1, and cyclooxygenase (COX)-2) to reduce immunosuppression. Moreover, MTE-administrated alleviated intestinal mucositis and improved the prognostic indexes compared with the 5-FU group. Notably, the ability of low-dose MTE to regulate immune cells and the function of the tumor microenvironment was higher than that of high-dose. Generally, MTE as an immunomodulator presents great potential to strengthen anti-CRC activity.