Anti-neoplastic and immunomodulatory potency of co-treatment based on bovine lactoferrin and/or muramyl dipeptide in tumor-bearing mice

Abstract

The current study investigates anti-neoplastic and immunomodulatory activities of co-treatment based on bovine lactoferrin (bLF) and/or muramyl dipeptide (MDP) with or without cisplatin (Cis) in tumor-bearing mice. In the present study, bLF (100 mg/kg; orally) and MDP (0.5 mg/kg; subcutaneously) was administered alone or together. MDP or bLF was co-treated with Cis (1 mg/kg; intraperitoneally) in mice-bearing Ehrlich solid carcinoma. Tumor size, tumor mass proliferation, apoptosis using immunohistochemistry, the alteration in spleen cell proliferation, phenotype using flow cytometry and white blood cells total and differential counts were detected. Treatment with Cis or (bLF and MDP) significantly reduced tumor size, upregulated the pro-apoptotic p53 expression and downregulated the anti-apoptotic Bcl-2 and proliferative marker PCNA expression compared to non-treated tumor-bearing animals. Moreover, co-treatment of MDP and Cis significantly potentiated the reduction of the tumor size, downregulated the Bcl-2 and PCNA expression and upregulated the p53 expression compared to Cis-treated animals. While bLF and Cis co-treatment positively controlled PCNA and p53 expression compared to tumor-bearing animals, it significantly potentiated the reduction of the tumor size and downregulated the Bcl-2 expression compared to Cis-treated animals. Co-treatment of (bLF and MDP), (bLF and Cis) or (MDP and Cis) increased the spleen cell proliferation and altered the immunological profile of the CD3+CD4+, CD3+CD8+, CD3+CD4+CD69+, CD3+CD8+CD69+ and CD11b+Ly6G+ cells to achieve better immune response against tumor. In conclusion, co-treatments based on bLF and/or MDP are promising therapies against cancer, through their potency to control proliferation, enhance apoptosis and improve the immune status against tumor cells.

Anti-proliferative and immunomodulatory potencies of cinnamon oil on Ehrlich ascites carcinoma bearing mice

“…Similar to earlier findings, an escape strategy of the tumour cells, the tumour microenvironment was characterised by the proliferation of particular cell types such as regulatory T cells (CD4 + CD25 + ) in order to suppress the protective antitumor immunity 47 – 53 . In accordance , Ibrahim et al 54 clarified that tumor development was linked to a decrease in the percentage of splenic CD3 + CD8 + cell population in Ehrlich solid tumor bearing mice. Furthermore, cinnamon effectively restored the balance of T-cell subsets by promoting the proliferation of T helper-1 and T cytotoxic 1 while reducing the proliferation of regulatory T cells in SLTBI mice and augmenting the IFN-γ production and strengthening the antitumor effect against lung metastasis of melanoma in SLTBI mice 55 .…”

Muramyl dipeptide-based analogs as potential anticancer compounds: Strategies to improve selectivity, biocompatibility, and efficiency

“…Ibrahim et al. ( 46 ) investigated the antitumor and immunomodulatory effects of co-treatment based on MDP with or without Cis and bovine lactoferrin (bLF) in mice with Ehrlich solid tumor (ESTs). It was concluded that the combination of MDP and bLF could stimulate an innate but also an adaptive immune response, and this could lead to an optimal therapeutic immune response in an Ehrlich carcinoma murine model.…”

Lactoferrin may inhibit the development of cancer via its immunostimulatory and immunomodulatory activities

“…Lf has been confirmed to enhance the adaptive immune response and is an effective anti-inflammatory drug (63). Although its molecular mechanism still needs to be revealed, researchers have found that both hLf and bLf can enter the host cell nucleus and bind to DNA to regulate gene expression, thereby exerting their anti-inflammatory activity (64).…”