Prostate
cancer (PCa) is the second most common cancer in males worldwide and is the
most frequent cancer in men over 65 years old. PCa is the sixth most common
cancer in Taiwan. Although surgery is often successful for organ-confined PCa,
androgen ablation therapy is the primary treatment for metastatic PCa. However,
most PCa patients receiving androgen ablation therapy will ultimately develop
castration-resistant prostate cancer (CRPC) within 1 to 3 years, with a median overall
survival time of 1 to 2 years after relapse. Although docetaxel, enzalutamide, and
abiraterone are usually applied to treatment of CRPC, these drugs show little
effect on prolonging survival, and the majority of patients develop resistance
to these drugs within months.
Honeybee
propolis has been reported to exhibit anti-oxidant, anti-bacteria, anti-viral,
anti-cancer, and immune modulation effects. Caffeic acid phenethyl ester (CAPE)
is a main bioactive component extracted from honeybee hive propolis; it
accounts for approximately 1 to 7% of the solid weight of propolis. The
research team of Dr. Chih-Pin Chuu from NHRI and Dr. Chuang-Rung Chang from National
Tsing Hua University investigated the possibility of using CAPE to suppress AR
signaling in PCa. Doctoral student Ying-Yu Kuo discovered that CAPE can
efficiently suppress downstream signaling of AT as well as reduce the PSA
secreted by PCa cells. She was surprised to find that CAPE treatment can
decrease the protein expression level of AR in PCa cells. She discovered that
CAPE treatment suppresses the protein abundance and activity of AKT and CDK1,
the two kinases responsible for phosphorylating AR on Ser81 and Ser213. The
reduction of phosphorylation on AR decreases the stability of AR, therefore
inducing the degradation of AR in PCa cells. CAPE works very differently than enzalutamide,
abiraterone, or casodex to inhibit the signaling and function of AR. The unique
mechanism of CAPE to enhance the degradation of AR protein implies the
possibility of using CAPE as a novel therapeutic agent for AR-related diseases,
such as prostate cancer, benign prostate hyperplasia (BPH), and androgenetic
alopecia. This study has been published in Cell Signaling and Communication.