Plant polyphenols aggravate liver metastases
Epidemiological studies suggest that vegetarian diets are associated with lower cancer incidence and mortality, an effect commonly attributed in part to plant-derived phytochemicals (PP). Although numerous in vitro experiments and investigations using immunodeficient rodent models report tumor-suppressive activities of PP, their impact on tumor progression in immunocompetent hosts remains insufficiently understood. Here, we examined the influence of a defined mixture of phytochemicals (PPM) sourced from various plants on the growth of colon cancer liver metastases in immunocompetent mice. Consistent with the prevailing literature, treatment of the murine colon cancer cell line MC38 with PPM significantly reduced cell proliferation and survival in vitro. Strikingly, however, administration of PPM to mice bearing MC38-derived hepatic metastases markedly accelerated tumor growth. Immunohistochemical analyses revealed a significantly increased accumulation of immune cells—specifically CD45? leukocytes and F4/80? macrophages—at the periphery of the metastatic lesions in PPM-treated animals. To assess the functional relevance of this inflammatory response, PPM was combined with the anti-inflammatory drug prednisolone. This intervention resulted in significantly reduced metastatic burden, supporting the notion that PPM exacerbates tumor progression through enhanced peritumoral inflammation. These findings highlight the importance of validating observations from cell culture and immunodeficient models in fully immunocompetent systems. They further emphasize that the immunomodulatory effects of plant phytochemicals warrant careful and comprehensive investigation.