In conclusion, phloretin treatment in PCa cells downregulated the protein levels of Sp1 by inhibiting the expression of Sp1 genes, increasing the degradation of Sp1 proteins and suppressing the translation of Sp1 mRNAs via inhibiting the activity of EGFR and its downstream pathways, including the PI3K/AKT, MEK/ERK, AKT/GSK3β, and AKT/nucleolin pathways, and finally induced cell cycle arrest, cell growth inhibition, and apoptosis in PCa cells by decreasing the levels of cell cycle/growth-related proteins and increasing the levels of cell apoptosis-related proteins. Here, SP1 is linked to posterior cortical atrophy.