Substance in honeybee propolis may be useful in treating prostate cancer: new study

November 11, 2019

 

Dysregulation of androgen receptor signaling is one of the causes promoting the development of prostate cancer, benign prostate hyperplasia (BPH), and androgenetic alopecia. The prescription drugs for these diseases either block the production of androgen or inhibit the binding between androgen and androgen receptor (AR). However, none of them can cause degradation of AR. This study demonstrated that caffeic acid phenethyl ester (CAPE) reduces phosphorylation on AR and thus causes degradation of AR, suggesting the possibility of using CAPE as a therapeutic agent for AR-related diseases.

 

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.

For the full text of the publication in Cell Signaling and Communication, visit https://biosignaling.biomedcentral.com/articles/10.1186/s12964-019-0404-9

 

Figure. 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.

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