Zapotin, a Phytochemical Present in a Mexican Fruit, Prevents Colon Carcinogenesis

Abstract Zapotin (5,6,2′,6′-tetramethoxyflavone), found in the tropical fruit zapote blanco (Casimiroa edulis), is consumed in many parts of the world, including Central America and Asia. Previously, we have demonstrated in vitro chemopreventive activity of extracts derived from the seeds of C. edulis. In the present study, we examined the effects of natural and synthetic zapotin in SW480, SW620, and HT-29 colon cancer cell lines and on the generation of aberrant crypt foci (ACF) using mice. Zapotin treatment (IC50 = 2.74 × 10−7 M) resulted in a marked suppression of cell proliferation in the HT-29 cells. Cell cycle analysis demonstrated a significant accumulation of cells in the G2-M phase, with a concomitant decrease of cells in the G0-G1 phase, after treatment with zapotin (molecular weight = 342.35 g/mol; 1 μ M for 18, 24, and 48 h). Zapotin treatment enhanced apoptosis in all of the colon cancer cell lines studied. For the study of ACF, 5-wk-old CF-1 mice were given subcutaneous injections of azoxyme...