CDKN1B and prostate carcinoma: Similarly, Tam et al. demonstrated in 22Rv1 prostate cancer cells that via the MT1, melatonin reduced proliferation through co-activation of parallel PKC and protein kinase A (PKA) cascades that resulted in the upregulation of p27Kip1 [55], another CDK inhibitor with targets such as G1 cyclin E-CDK2 and cyclin D-CDK4/6 [56].