Caffeic Acid Phenethyl Ester Causes p21Cip1 Induction, Akt Signaling Reduction, and Growth Inhibition in PC-3 Human Prostate Cancer Cells

Abstract

Caffeic acid phenethyl ester (CAPE) treatment suppressed proliferation, colony formation, and cell cycle progression in PC-3 human prostate cancer cells. CAPE decreased protein expression of cyclin D1, cyclin E, SKP2, c-Myc, Akt1, Akt2, Akt3, total Akt, mTOR, Bcl-2, Rb, as well as phosphorylation of Rb, ERK1/2, Akt, mTOR, GSK3α, GSK3β, PDK1; but increased protein expression of KLF6 and p21Cip1. Microarray analysis indicated that pathways involved in cellular movement, cell death, proliferation, and cell cycle were affected by CAPE. Co-treatment of CAPE with chemotherapeutic drugs vinblastine, paclitaxol, and estramustine indicated synergistic suppression effect. CAPE administration may serve as a potential adjuvant therapy for prostate cancer.

Synthesis of Caffeic Acid Phenethyl Ester Derivatives, and Their Cytoprotective and Neuritogenic Activities in PC12 Cells

“…Their cytoprotective activities were much better than those of the parent compound CAPE under the same concentrations. Compounds 3, 4, 12, 13, 15, 16 and 19 showed similar protective capabilities to CAPE within the range of 62.9−81.1% at 4 nM, while compounds 1−4, 6,7,9,10,12,13,16,19, and 20 possessed equivalent protective effects as CAPE within the range 61.9−93.9% at 40 nM (Figure 1). Other CAPE derivatives demonstrated poorer activities against H 2 O 2 -indued cytotoxicity (data not shown).…”

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

“…CAPE is a well known NF-κB inhibitor at concentrations of 50 μM to 80 μM by preventing the translocation of p65 unit of NF-κB and the binding between NF-κB and DNA [17]. We previously reported that CAPE dosage dependently suppressed the proliferation of androgen-dependent LNCaP 104-S and AR-negative PC-3 cells [18, 19]. Administration of CAPE by gavage significantly inhibited the tumor growth of LNCaP and PC-3 xenografts in nude mice [18–20].…”

“…We previously reported that CAPE dosage dependently suppressed the proliferation of androgen-dependent LNCaP 104-S and AR-negative PC-3 cells [18, 19]. Administration of CAPE by gavage significantly inhibited the tumor growth of LNCaP and PC-3 xenografts in nude mice [18–20]. We discovered that CAPE treatment inhibited cell growth and induced G1 cell cycle arrest by suppressing c-Myc and Akt-related protein signaling networks in LNCaP 104-S and PC-3 cells [18–20].…”

“…Administration of CAPE by gavage significantly inhibited the tumor growth of LNCaP and PC-3 xenografts in nude mice [18–20]. We discovered that CAPE treatment inhibited cell growth and induced G1 cell cycle arrest by suppressing c-Myc and Akt-related protein signaling networks in LNCaP 104-S and PC-3 cells [18–20]. However, the protein expression profile and response to treatment of chemotherapy drugs or kinase inhibitors was quite different between LNCaP 104-R1 and LNCaP 104-S cells [21].…”

Terrestrosin D, a Steroidal Saponin from <b><i>Tribulus terrestris</i></b> L., Inhibits Growth and Angiogenesis of Human Prostate Cancer in vitro and in vivo

“…Androgen ablation therapy is an effective treatment during the early stages of PCa; however, it is associated with several side effects including loss of libido and bone density as well as cardiovascular morbidity [2]. Moreover, most PCa ultimately progresses to metastatic castration-resistant PCa (CRPC) after hormone therapy [3,4,5]. Although clinical trial data have shown that enzalutamide and abiraterone acetate significantly prolong overall survival in patients with metastatic CRPC, there is currently no systemic and effective therapy for CRPC [5,6,7].…”