Modulatory effects of phytoestrogens, fresh soy milk, and annexin A1 on cell cycle regulation and apoptotic pathways in human leukemic cells and peripheral blood mononuclear cells

Phytoestrogens, plant-derived compounds with estrogen-like activity, along with fresh soy milk and Annexin A1, an endogenous protein, exhibit notable anti-cancer properties. This study investigated their effects on apoptosis and cell cycle regulation in human leukemic cell lines (K562, Jurkat, U937) and normal peripheral blood mononuclear cells (PBMCs). Coumestrol, genistein, and Annexin A1 induced statistically significant effects (p < 0.05), primarily causing G2/M phase arrest, followed by G0/G1 arrest, with a modest (∼3–5 %) increase in S-phase cells. In K562 cells, arrest correlated with upregulation of cyclins E1 and A2, and downregulation of cyclin B1, while cyclin D1 showed an inverse pattern. In Jurkat and U937 cells, cyclins D1, E1, A2, and B1 were consistently downregulated. Cell cycle arrest was regulated by p21 independently of p53 in all treated cell lines. Caspase activation patterns varied: caspases-9 and -8 were activated in K562 and U937 cells, while caspase-3 activation occurred only in genistein-treated Jurkat cells. Bcl-2 was upregulated in most treatments, except in coumestrol-treated K562 and genistein-treated Jurkat cells. PBMCs showed S and G2/M arrest without apoptosis or caspase activation. These findings demonstrate the statistically supported (p < 0.05) anti-cancer potential of these agents and suggest their promise as alternative leukemia treatments by modulating distinct apoptotic and cell cycle-regulatory pathways.