Butyrate-associated antiproliferative and antitumor effects of

Introduction: Recent work has shown that Methods: We characterized Results: ElCFS preferentially inhibited the proliferation of human HCT116 and murine CT26 CRC cells while having little effect on non-malignant CCD 841 CoN colonic cells. The activity persisted after heat and enzymatic treatments, and pH-dependent liquid-liquid extraction indicated that a small organic acid was a major bioactive component. High-performance liquid chromatography detected 13.77 mM butyrate and 23.33 mM acetate in ElCFS. At approximately the concentration delivered by 10% ElCFS, sodium butyrate (NaB; 1.3 mM) produced comparable antiproliferative activity, whereas sodium acetate did not, supporting butyrate as a major candidate contributor to ElCFS activity. ElCFS and approximately concentration-matched NaB increased histone H3 acetylation, consistent with histone deacetylase inhibition, and induced apoptosis, as evidenced by PARP and caspase-3 cleavage and p53 phosphorylation. Their antiproliferative effects were markedly attenuated under glucose-depleted conditions. In a CT26 syngeneic tumor model, peritumoral administration of ElCFS reduced tumor growth, indicating that secreted Discussion: Together, these findings link