Gum mastic inhibits the expression and function of the androgen receptor in prostate cancer cells.
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.
He
Mei-Lan
ML
Institute of Cancer Research, Life Science School, Tongji University, Shanghai, People's Republic of China.
Yuan
Hui-Qing
HQ
Jiang
An-Li
AL
Gong
Ai Yu
AY
Chen
Wei-Wen
WW
Zhang
Peng-Ju
PJ
Young
Charles Y F
CY
Zhang
Jian-Ye
JY
D000728:Androgens / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000502:physiology; D018450:Disease Progression; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D000069997:Mastic Resin; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000503:physiopathology* / Q000517:prevention & control; D011485:Protein Binding / Q000187:drug effects; D011944:Receptors, Androgen / Q000032:analysis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D012116:Resins, Plant / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020840:Tissue Kallikreins / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D000728:Androgens; D018398:Homeodomain Proteins; D000069997:Mastic Resin; C491178:NKX3-1 protein, human; D011944:Receptors, Androgen; D012116:Resins, Plant; D014157:Transcription Factors; D019938:Cyclin D1; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen