Anti-tumor effect of flavonoids isolated from Bidens Pilosa L. by regulating the activity of myeloid-derived suppressor cells within the tumor microenvironment in mice.

Ethnopharmacological relevance: Colon cancer is one of the most common malignant tumors worldwide. Bidens pilosa L., an annual herb of the Asteraceae, has long been used to treat inflammatory-related illnesses, including cancer. As a population of immunosuppressive cells in the TME, MDSCs play a pivotal role in tumorigenesis and progression, and the effect of B. pilosa on MDSCs has rarely been reported.

Aim of study: To investigate the anti-tumor effect of a mixture of two flavonoids, MTF, isolated from B. pilosa, which showed immunotherapeutic activity in regulating the function of MDSCs in colon cancer.

Materials and methods: The regulatory effects of the flavonoid MTF on MDSCs differentiation and immune function were tested by qRT-PCR and flow cytometry. Its underlying immunotherapeutic mechanism, cytotoxicity, and anti-angiogenic activity were investigated using SIE luciferase/Western blot, CCK-8/apoptosis, and MDSC-HUVEC co-culture assays, respectively. The in vivo anti-tumor activity of MTF was subsequently investigated in both CT26. WT and CT26. WT/MDSCs syngeneic models.

Results: MTF and its components effectively depleted MDSCs by inhibiting their differentiation and inducing apoptosis, thereby restoring suppressed CD4⁺ T cell function. In vivo, MTF not only reduced intratumoral MDSCs but also counteracted MDSC-driven angiogenesis, leading to inhibited tumor growth and enhanced sensitivity to 5-FU treatment.

Conclusion: Flavonoid MTF showed a good anti-tumor effect in mice by regulating MDSCs activity within the TME, which contributes to the clinical use of this traditional herb.