Gum mastic inhibits the expression and function of the androgen receptor in prostate cancer cells

• Published in: Cancer Vol. 106; no. 12; pp. 2547 - 2555
• Main Authors: He, Mei‐Lan, Yuan, Hui‐Qing, Jiang, An‐Li, Gong, Ai Yu, Chen, Wei‐Wen, Zhang, Peng‐Ju, Young, Charles Y. F., Zhang, Jian‐Ye
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.06.2006; Wiley-Liss
• Subjects: androgen receptor; Androgens - pharmacology; androgen‐regulated gene; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclin D1 - genetics; Cyclin D1 - physiology; Disease Progression; Electrophoretic Mobility Shift Assay; Gene Expression Regulation, Neoplastic - drug effects; gum mastic; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Humans; Male; Mastic Resin; Medical sciences; Neoplasms, Hormone-Dependent - chemistry; Neoplasms, Hormone-Dependent - genetics; Neoplasms, Hormone-Dependent - pathology; Neoplasms, Hormone-Dependent - physiopathology; Nephrology. Urinary tract diseases; Promoter Regions, Genetic - genetics; prostate cancer cell line; Prostate-Specific Antigen - analysis; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - genetics; Prostatic Neoplasms - physiopathology; Prostatic Neoplasms - prevention & control; Protein Binding - drug effects; Receptors, Androgen - analysis; Receptors, Androgen - drug effects; Receptors, Androgen - genetics; Receptors, Androgen - physiology; Resins, Plant - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Tissue Kallikreins - genetics; Tissue Kallikreins - physiology; Transcription Factors - genetics; Transcription Factors - physiology; Transcription, Genetic - drug effects; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urinary system disease; Prostate disease; Androgen; Malignant tumor; Cancerology; Gene; androgen-regulated gene; Established cell line; Androgen receptor; gum mastic; Genetics; prostate cancer cell line; Inhibitor; Sex steroid hormone; Male genital diseases; Prostate cancer; Tumor cell; Gum; Hormonal receptor
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21935

Accumulating evidence suggests that the androgen receptor (AR) may play an important role in the development and progression of prostate cancer. To find new, useful compounds that effectively may attenuate the function of AR in prostate cancer cells, the authors investigated the effect of gum mastic, a natural resin, on AR activity. An androgen‐responsive prostate cancer cell line LNCaP was used as a model for this study. Gene transfer, reverse transcriptase‐polymerase chain reaction analysis, electrophoretic mobility shift assay, and Western blot analysis were used to test the effect of gum mastic on the expression and function of the AR. To demonstrate the inhibitory effect of gum mastic on the function of the AR, the expression of androgen‐regulated genes, including prostate‐specific antigen (PSA), human kallikrein 2 (hK2), and NKX3.1 were measured. In addition, transient transfection assays with the PSA promoter and the AR promoter also were used to test the effects of mastic. The results showed that gum mastic inhibited the expression of the AR at the transcriptional level, resulting in the down‐regulation of both AR messenger RNA and protein levels. Therefore, the function of the AR was inhibited, as reflected by the reduced expression of NKX3.1 and PSA and by androgen‐stimulated growth. Because gum mastic exhibited a strong in vitro potency to attenuate the expression and function of the AR, further investigation will be required to determine whether this naturally occurring substance has in vivo potency to inhibit prostate cancer development. Cancer 2006. © 2006 American Cancer Society. The androgen receptor plays a critical role in the development and progression of prostate cancer. The results of this article indicated that gum mastic exhibited strong in vitro potency to attenuate the androgen receptor activity. Further investigation will be required to determine whether gum mastic has in vivo potency to inhibit the development of prostate cancer.