Abstract
Caffeic acid phenethyl ester (CAPE) is a bioactive component derived from honeybee hive propolis. We previously showed that treatment with CAPE suppresses growth of androgen-dependent AR-positive LNCaP 104-S cells both in vitro and in vivo via inhibition of Akt and c-Myc signaling, thus causes G1 cell cycle arrest. Androgen ablation therapy is the primary treatment for metastatic prostate cancer (PCa). However, a majority of PCa patients receiving the androgen ablation therapy will ultimately develop recurrent castration-resistant prostate cancer (CRPC) within 1-3 years after treatment with a median overall survival time of 1-2 years after relapse. There is currently no effective therapy and new therapeutic targets are needed. The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. We have established AR-rich androgen-independent LNCaP 104-R1 cells derived from parental androgen-dependent LNCaP 104-S cells under androgen depleted condition. LNCaP 104-R1 cells mimic CRPC in patients. CAPE treatment caused G1 cell cycle arrest in 104-R1 cells and thus suppressed cell proliferation and tumor growth in nude mice. Micro-Western Array (MWA) is an antibody-based modified reverse phase array, which allows detecting protein expression level or phosphorylation status change of 96-384 different antibodies in 6-15 samples simultaneously. Using MWA platform, we found that CAPE reduced Akt-related proteins expression slightly, but decrease Skp2 abundance significantly, which may explain its larger resistance to CAPE treatment than 104-S cells. Overexpression of Skp2 blocked suppressive effect of CAPE. Co-treatment of CAPE with PI3K inhibitor LY294002 or Bcl-2 inhibitor ABT-737 both showed synergistic suppressive effects. Our finding suggested that CAPE treatment is a potential therapy for CRPC.
Published Version
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