國家衛生研究院 NHRI:Item 3990099045/8648
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    題名: Caffeic acid phenethyl ester induced cell cycle arrest and growth inhibition in androgen-independent prostate cancer cells via regulation of Skp2, p53, p21Cip1 and p27Kip1
    作者: Lin, HP;Lin, CY;Huo, C;Hsiao, PH;Su, LC;Jiang, SS;Chan, TM;Chang, CH;Chen, LT;Kung, HJ;Wang, HD;Chuu, CP
    貢獻者: National Institute of Cancer Research;Institute of Molecular and Genomic Medicine;Institute of Cellular and Systems Medicine
    摘要: Prostate cancer (PCa) patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant prostate cancer (CRPC) within 1-3 years. Treatment with caffeic acid phenethyl ester (CAPE) suppressed cell survival and proliferation via induction of G1 or G2/M cell cycle arrest in LNCaP 104-R1, DU-145, 22Rv1, and C4-2 CRPC cells. CAPE treatment also inhibited soft agar colony formation and retarded nude mice xenograft growth of LNCaP 104-R1 cells. We identified that CAPE treatment significantly reduced protein abundance of Skp2, Cdk2, Cdk4, Cdk7, Rb, phospho-Rb S807/811, cyclin A, cyclin D1, cyclin H, E2F1, c-Myc, SGK, phospho-p70S6kinase T421/S424, phospho-mTOR Ser2481, phospho-GSK3alpha Ser21, but induced p21Cip1, p27Kip1, ATF4, cyclin E, p53, TRIB3, phospho-p53 (Ser6, Ser33, Ser46, Ser392), phospho-p38 MAPK Thr180/Tyr182, Chk1, Chk2, phospho-ATM S1981, phospho-ATR S428, and phospho-p90RSK Ser380. CAPE treatment decreased Skp2 and Akt1 protein expression in LNCaP 104-R1 tumors as compared to control group. Overexpression of Skp2, or siRNA knockdown of p21Cip1, p27Kip1, or p53 blocked suppressive effect of CAPE treatment. Co-treatment of CAPE with PI3K inhibitor LY294002 or Bcl-2 inhibitor ABT737 showed synergistic suppressive effects. Our finding suggested that CAPE treatment induced cell cycle arrest and growth inhibition in CRPC cells via regulation of Skp2, p53, p21Cip1, and p27Kip1.
    日期: 2015-03
    關聯: Oncotarget. 2015 Mar;6(9):6684-6707.
    Link to: http://dx.doi.org/10.18632/oncotarget.3246
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000352793800017
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84927134815
    顯示於類別:[陳立宗] 期刊論文
    [江士昇] 期刊論文
    [龔行健] 期刊論文
    [褚志斌] 期刊論文
    [張中和] 期刊論文

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