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

• DOI: 10.18632/oncotarget.3246
• Publication Date: 2015-09-15T07:55:06Z
• Authors: Hui-Ping Lin; Ching-Yu Lin; Chieh Huo; Ping-Hsuan Hsiao; Liang-Cheng Su; Shih Sheng Jiang; Tzu-Min Chan; Chung-Ho Chang; Li-Tzong Chen; Hsing-Jien Kung; Horng-Dar Wang; Chih-Pin Chuu
• Keywords: Cyclin-Dependent Kinase Inhibitor p21; Male; 0301 basic medicine; Mice, Inbred BALB C; Dose-Response Relationship, Drug; Mice, Nude; Antineoplastic Agents; Drug Synergism; Phenylethyl Alcohol; G1 Phase Cell Cycle Checkpoints; 3. Good health; G2 Phase Cell Cycle Checkpoints; 03 medical and health sciences; Caffeic Acids; Cell Line, Tumor; Antineoplastic Combined Chemotherapy Protocols; Animals; Humans; Phosphatidylinositol 3-Kinase; Phosphorylation; Cyclin-Dependent Kinase Inhibitor p27; Cell Proliferation; Phosphoinositide-3 Kinase Inhibitors

// Hui-Ping Lin 1, * , Ching-Yu 2, Chieh Huo 3, Ping-Hsuan Hsiao 4, Liang-Cheng Su 2 Shih Sheng Jiang 1 Tzu-Min Chan 5, 6 Chung-Ho Chang Li-Tzong Chen Hsing-Jien Kung 7 Horng-Dar Wang 4 Chih-Pin Chuu 8, 9, 10, 11 National Institute of Cancer Research, Health Research Institutes, Miaoli, Taiwan, ROC Cellular and System Medicine, 3 Department Life Sciences, Central University, Taoyuan, Biotechnology, Tsing Hua Hsinchu City, 5 Medical Education China University Beigan Hospital, Yunlin, University-An Nan Tainan, Molecular Genomic Miaoli County, 8 Graduate Basic Science, Taichung, 9 Program for Aging, 10 Biotechnology Center, Chung Hsing Ph.D. in Environmental Occupational Kaohsiung These authors have contributed equally to this work Correspondence to: Chuu, e-mail: [e-mail] Keywords: Prostate cancer, caffeic acid phenethyl ester, cell cycle arrest, Skp2, p53 Received: September 18, 2014      Accepted: January 30, 2015      Published: February 16, 2015 ABSTRACT cancer (PCa) patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant prostate (CRPC) within 1–3 years. Treatment with ester (CAPE) suppressed survival proliferation via induction G1 or G2/M arrest LNCaP 104-R1, DU-145, 22Rv1, C4–2 CRPC cells. CAPE treatment also inhibited soft agar colony formation retarded nude mice xenograft growth 104-R1 We identified that significantly reduced protein abundance Cdk2, Cdk4, Cdk7, Rb, phospho-Rb S807/811, cyclin A, D1, H, E2F1, c-Myc, SGK, phospho-p70S6kinase T421/S424, phospho-mTOR Ser2481, phospho-GSK3α Ser21, but induced p21 Cip1 p27 Kip1 ATF4, E, p53, TRIB3, phospho-p53 (Ser6, Ser33, Ser46, Ser392), phospho-p38 MAPK Thr180/Tyr182, Chk1, Chk2, phospho-ATM S1981, phospho-ATR S428, phospho-p90RSK Ser380. decreased Skp2 Akt1 expression tumors as compared control group. Overexpression siRNA knockdown blocked suppressive effect treatment. Co-treatment PI3K inhibitor LY294002 Bcl-2 ABT737 showed synergistic effects. Our finding suggested inhibition cells regulation .