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p21(CIP1) Induces Apoptosis via Binding to BCL2 in LNCaP Prostate Cancer Cells Treated with MCS-C3, A Novel Carbocyclic Analog of Pyrrolopyrimidine

Title
p21(CIP1) Induces Apoptosis via Binding to BCL2 in LNCaP Prostate Cancer Cells Treated with MCS-C3, A Novel Carbocyclic Analog of Pyrrolopyrimidine
Author
류종석
Keywords
Prostate cancer; LNCaP cells; apoptosis; p21(CIP1); BCL2; ANDROGEN RECEPTOR; P21; EXPRESSION; P53; INDUCTION; MITOCHONDRIA; SANGIVAMYCIN; ASSOCIATION; INHIBITOR; CLEAVAGE
Issue Date
2016-01
Publisher
INT INST ANTICANCER RESEARCH
Citation
ANTICANCER RESEARCH, v. 36, No. 1, Page. 213-220
Abstract
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 p21(CIP1). The present study aimed to evaluate the cellular functions and underlying molecular mechanisms of p21(CIP1) on apoptotic induction in LNCaP cells treated with 6 mu M MCS-C3. Materials and Methods: Western blots, flow cytometric assay, immunoprecipitation, and transmission electron microscopy analysis were used to measure apoptotic induction in 6-mu M MCS-C3-treated LNCaP cells. Effects of MCS-C3 on gene expression of p21(CIP1) 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 p21(CIP1) in LNCaP cells. Moreover, this apoptotic induction was caused by direct binding of p21(CIP1) to anti-apoptotic B-cell lymphoma 2 (BCL2) protein, and antagonizing BCL2 function. In addition, MCS-C3-mediated apoptotic induction, and up-regulation of p21(CIP1) were almost completely blocked by the treatment of androgen-esponsive LNCaP cells with flutamide, an androgen receptor (AR) antagonist. Conclusion: We identified that induction of intrinsic apoptosis in LNCaP cells by 6 mu M 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 p21(CIP1) on apoptotic induction via direct binding to BCL2 in LNCaP cells treated with 6 mu M MCS-C3.
URI
http://ar.iiarjournals.org/content/36/1/213.fullhttp://repository.hanyang.ac.kr/handle/20.500.11754/102069
ISSN
0250-7005; 1791-7530
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > ETC
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