Influence of the Chemotherapeutic Agent Mitomycin C on In Vitro Dendritic Cell Maturation and Interleukin-12 Production in a Colorectal Cancer Model.

Abstract

Background: Antitumor-targeting drugs can stimulate dendritic cells (DCs) indirectly through the shedding of dying tumor cells as part of what is referred to as a "danger signal". Although chemotherapeutic agents have been shown to kill dendritic cells (DCs), the effects of low, non-cytotoxic doses on DC function have not been studied.

Objective: To investigate the impact of various concentrations of mitomycin C at low, non-cytotoxic doses on the maturation of DCs.

Methods: THP-1 monocytes were differentiated into immature dendritic cells using IL-4 and GM-CSF. HCT116 colorectal cancer cells were treated with mitomycin C at concentrations ranging from 10 to 80 nM and co-cultured with undifferentiated dendritic cells. The expression of co-stimulatory molecules (CD11c, CD80, CD83, CD86, HLA-DR, CD14) and IL-12p70 secretion were measured.

Results: Different dosages of Mitomycin C-treated HCT116 cells enhanced the maturation of dendritic cell markers (CD80, CD83, CD86, HLA-DR), but reduced CD14 levels (p< 0.01). While increasing the Mitomycin C dose to 80 nM further upregulated HLA-DR and CD86 expression, the release of IL-12 was highest a 50 nM concentration of mitomycin C (686.7 ± 125.7 pg/mL compared to 263.8 ± 4.8 pg/mL in controls; p < 0.05). IL-12 levels were not significantly increased even with 30 nM Mitomycin C.

Conclusion: Low concentrations of Mitomycin C contributed to an increase in dendritic cellmaturation and an increase in the expression of co-stimulatory molecules (CD80, CD86, CD83, and HLA-DR), along with the secretion of cytokines such as IL-12p70, IL-2, and GM-CSF.