Penta-O-galloyl-β-D-glucose Suppresses Prostate Cancer Bone Metastasis by Transcriptionally Repressing EGF-Induced MMP-9 Expression

被引:52
作者
Kuo, Po-Tsun [2 ]
Lin, Tsung-Pang [3 ]
Liu, Liang-Chih [2 ,4 ]
Huang, Chi-Hung [2 ]
Lin, Jen-Kun [3 ]
Kao, Jung-Yie [2 ]
Way, Tzong-Der [1 ]
机构
[1] China Med Univ, Sch Biol Sci & Technol, Coll Life Sci, Taichung 40402, Taiwan
[2] Natl Chung Hsing Univ, Inst Biochem, Coll Life Sci, Taichung 40227, Taiwan
[3] Natl Taiwan Univ, Inst Biochem & Mol Biol, Coll Med, Taipei 10764, Taiwan
[4] FongYuan Hosp, Dept Hlth Execut Yuan, Dept Surg, Taichung, Taiwan
关键词
5GG; MMP-9; EGFR; JNK; invasion; prostate cancer; EPIDERMAL-GROWTH-FACTOR; NF-KAPPA-B; FACTOR-RECEPTOR; TUMOR-GROWTH; DOWN-REGULATION; IN-VITRO; CELLS; INVASION; PROGRESSION; ACTIVATION;
D O I
10.1021/jf803725h
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of cancer-related death of men in the United States. Epidermal growth factor (EGF) generated from bone tissue contributes to prostate cancer metastasis through stimulating matrix metalloproteinase (MMP) secretions from prostate cancer cells. In this study, in vitro invasion assay was performed by incubating penta-O-galloyl-beta-D-glucose (5GG) at various concentrations with 2 x 10(4) PC-3 cells for 48 h. The anti-invasive and cytotoxic effects of 5GG were found and evaluated on the human androgen-independent prostate cancer PC-3 cell line by MTT assays and Western blot analyses. 5GG inhibited the EGF-induced cell invasiveness and MMP-9 expression in a dose- and time-dependent manner by reducing the MMP-9 transcriptional activity. To explore the mechanisms for the 5GG-mediated regulation of MMP-9, we further examined the effects of 5GG on transcription factors, including NF-kappa B, AP-1, and mitogen-activated protein kinase (MAPK) activities. The results showed that 5GG suppressed the EGF-incluced NF-kappa B nuclear translocation and also abrogated the EGF-incluced activation of c-jun N-terminal kinase (JNK), an upstream modulator of NF-kappa B. Moreover, we showed that 5GG reduced EGFR expression through the proteasome pathway. These results suggest that 5GG may exert at least part of its anti-invasive effect in androgen-independent prostate cancer by controlling MMP-9 expression through the suppression of the EGFR/JNK pathway. Finally, 5GG suppresses invasion and tumorigenesis in nude mice treatment with intratibia injection of PC-3 cells. These in vitro and in vivo results suggest that 5GG may be a therapeutic candidate for the treatment of advanced prostate cancer.
引用
收藏
页码:3331 / 3339
页数:9
相关论文
共 31 条
[1]   Heparin-binding epidermal growth factor-like growth factor stimulates androgen-independent prostate tumor growth and antagonizes androgen receptor function [J].
Adam, RM ;
Kim, J ;
Lin, JQ ;
Orsola, A ;
Zhuang, LY ;
Rice, DC ;
Freeman, MR .
ENDOCRINOLOGY, 2002, 143 (12) :4599-4608
[2]   Ligand-induced lysosomal epidermal growth factor receptor (EGFR) degradation is preceded by proteasome-dependent EGFR de-ubiquitination [J].
Alwan, HAJ ;
van Zoelen, EJJ ;
van Leeuwen, JEM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (37) :35781-35790
[3]   NFκB:: A pivotal transcription factor in prostate cancer metastasis to bone [J].
Andela, VB ;
Gordon, AH ;
Zotalis, G ;
Rosier, RN ;
Goater, JJ ;
Lewis, GD ;
Schwarz, EM ;
Puzas, JE ;
O'Keefe, RJ .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2003, (415) :S75-S85
[4]   Molecular insights into prostate cancer progression: The missing link of tumor microenvironment [J].
Chung, LWK ;
Baseman, A ;
Assikis, V ;
Zhau, HE .
JOURNAL OF UROLOGY, 2005, 173 (01) :10-20
[5]   Therapeutic potential of curcumin in prostate cancer - IV: Interference with the osteomimetic properties of hormone refractory C4-2B prostate cancer cells [J].
Dorai, T ;
Dutcher, JP ;
Dempster, DW ;
Wiernik, PH .
PROSTATE, 2004, 60 (01) :1-17
[6]  
Festuccia C, 1998, INT J CANCER, V75, P418, DOI 10.1002/(SICI)1097-0215(19980130)75:3<418::AID-IJC16>3.0.CO
[7]  
2-4
[8]   HER2/HER3 heterodimers in prostate cancer: Whither HER1/EGFR? [J].
Freeman, MR .
CANCER CELL, 2004, 6 (05) :427-428
[9]   Green tea: Health benefits as cancer preventive for humans [J].
Fujiki, H .
CHEMICAL RECORD, 2005, 5 (03) :119-132
[10]   Mechanisms of the regulation of EGF receptor gene expression by calcitriol and parathyroid hormone in UMR 106-01 cells [J].
González, EA ;
Disthabanchong, S ;
Kowalewski, R ;
Martin, KJ .
KIDNEY INTERNATIONAL, 2002, 61 (05) :1627-1634