Indirubin derivatives that were potent GSK-3β inhibitors (relative to CDK1) stimulated LNCaP cell proliferation and other androgenic responses, suggesting (in a cancer treatment context) these compounds may increase AR-dependent prostate cancer growth if not used within an appropriate therapeutic dose-range.
These results indicate that the FOXO1-derived peptide FO1-6nls can restore FOXO1's tumor suppressor function by specifically opposing CDK1/2-mediated phosphorylation and inhibition of FOXO1 and hence may have a therapeutic potential for the treatment of PCa.
Moreover, these results indicate that increased Cdk1 activity is a mechanism for increasing AR expression and stability in response to low androgen levels in androgen-independent PCas, and that Cdk1 antagonists may enhance responses to androgen-deprivation therapy.
Additional data shows that adenoviral delivery of antisense CaSm inhibits the growth of prostate cancer cell lines by altering cell cycle progression, and is associated with reduced expression of cyclin B1 and CDK1 proteins.