TY - JOUR T1 - p21<sup>CIP1</sup> Induces Apoptosis <em>via</em> Binding to BCL2 in LNCaP Prostate Cancer Cells Treated with MCS-C3, A Novel Carbocyclic Analog of Pyrrolopyrimidine JF - Anticancer Research JO - Anticancer Res SP - 213 LP - 220 VL - 36 IS - 1 AU - KO-WOON CHOI AU - HYEWON SUH AU - HA LIM OH AU - CHONGSUK RYOU AU - CHUL-HOON LEE Y1 - 2016/01/01 UR - http://ar.iiarjournals.org/content/36/1/213.abstract N2 - Background: Previously, we synthesized a new carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside, designated MCS-C3. Recently, we found that LNCaP androgen-responsive prostate cancer cells treated with MCS-C3 rapidly undergo intrinsic apoptosis through dramatic up-regulation of p21CIP1. The present study aimed to evaluate the cellular functions and underlying molecular mechanisms of p21CIP1 on apoptotic induction in LNCaP cells treated with 6 μM MCS-C3. Materials and Methods: Western blots, flow cytometric assay, immunoprecipitation, and transmission electron microscopy analysis were used to measure apoptotic induction in 6-μM MCS-C3-treated LNCaP cells. Effects of MCS-C3 on gene expression of p21CIP1 were measured by semi-quantitative real-time polymerase chain reaction, and small interfering RNA transfection. Results: MCS-C3 induced appreciable caspase-dependent apoptosis associated with the significant up-regulation of p53-dependent p21CIP1 in LNCaP cells. Moreover, this apoptotic induction was caused by direct binding of p21CIP1 to anti-apoptotic B-cell lymphoma 2 (BCL2) protein, and antagonizing BCL2 function. In addition, MCS-C3-mediated apoptotic induction, and up-regulation of p21CIP1 were almost completely blocked by the treatment of androgen-responsive LNCaP cells with flutamide, an androgen receptor (AR) antagonist. Conclusion: We identified that induction of intrinsic apoptosis in LNCaP cells by 6 μM MCS-C3 is associated not only with p53 activation but also with mediation of AR. In the present study, we identified the cellular functions and underlying molecular mechanisms of p53-dependent and AR-associated p21CIP1 on apoptotic induction via direct binding to BCL2 in LNCaP cells treated with 6 μM MCS-C3. ER -