The natural agents isoflavone and 3,3′-Diindolylmethane inhibit the differentiation of osteoblasts and osteoclasts in a prostate cancer co-culture system, in part, via a downregulated AKT in the context of the homeobox protein Nkx-3.1 (NKX3-1)/AKT/cyclin-dependent kinase inhibitor 1B (p27) axis. Here, CDKN1B is linked to prostate carcinoma.