title: Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis.
abstract: Curcumin has been shown to possess potent chemopreventive and antitumor effects on prostate cancer. However, the molecular mechanism involved in curcumin's ability to suppress prostate cancer cell invasion, tumor growth, and metastasis is not yet well understood. In this study, we have shown that curcumin can suppress epidermal growth factor (EGF)- stimulated and heregulin-stimulated PC-3 cell invasion, as well as androgen-induced LNCaP cell invasion. Curcumin treatment significantly resulted in reduced matrix metalloproteinase 9 activity and downregulation of cellular matriptase, a membrane-anchored serine protease with oncogenic roles in tumor formation and invasion. Our data further show that curcumin is able to inhibit the induction effects of androgens and EGF on matriptase activation, as well as to reduce the activated levels of matriptase after its overexpression, thus suggesting that curcumin may interrupt diverse signal pathways to block the protease. Furthermore, the reduction of activated matriptase in cells by curcumin was also partly due to curcumin's effect on promoting the shedding of matriptase into an extracellular environment, but not via altering matriptase gene expression. In addition, curcumin significantly suppressed the invasive ability of prostate cancer cells induced by matriptase overexpression. In xenograft model, curcumin not only inhibits prostate cancer tumor growth and metastasis but also downregulates matriptase activity in vivo. Overall, the data indicate that curcumin exhibits a suppressive effect on prostate cancer cell invasion, tumor growth, and metastasis, at least in part via downregulating matriptase function.
authors: Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, R817, 8F, No. 1, Section 1, Jen-Ai Rd., Taipei, Taiwan.
authors: Tai-Shan
authors: TS
authors: Cheng
authors: Wen-Chi
authors: WC
authors: Chen
authors: Ya-Yun
authors: YY
authors: Lin
authors: Chin-Hsien
authors: CH
authors: Tsai
authors: Chia-I
authors: CI
authors: Liao
authors: Hsin-Yi
authors: HY
authors: Shyu
authors: Chun-Jung
authors: CJ
authors: Ko
authors: Sheue-Fen
authors: SF
authors: Tzeng
authors: Chun-Yin
authors: CY
authors: Huang
authors: Pan-Chyr
authors: PC
authors: Yang
authors: Pei-Wen
authors: PW
authors: Hsiao
authors: Ming-Shyue
authors: MS
authors: Lee
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D064593:Heterografts; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D004815:Epidermal Growth Factor; D012697:Serine Endopeptidases; C485596:ST14 protein, human; D003474:Curcumin