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Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis.
Cancer Prev Res (Phila) 2013; 6(5):495-505CP

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+Show Affiliations

Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, R817, 8F, No. 1, Section 1, Jen-Ai Rd., Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23466486

Citation

Cheng, Tai-Shan, et al. "Curcumin-targeting Pericellular Serine Protease Matriptase Role in Suppression of Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis." Cancer Prevention Research (Philadelphia, Pa.), vol. 6, no. 5, 2013, pp. 495-505.
Cheng TS, Chen WC, Lin YY, et al. Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis. Cancer Prev Res (Phila). 2013;6(5):495-505.
Cheng, T. S., Chen, W. C., Lin, Y. Y., Tsai, C. H., Liao, C. I., Shyu, H. Y., ... Lee, M. S. (2013). Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis. Cancer Prevention Research (Philadelphia, Pa.), 6(5), pp. 495-505. doi:10.1158/1940-6207.CAPR-12-0293-T.
Cheng TS, et al. Curcumin-targeting Pericellular Serine Protease Matriptase Role in Suppression of Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis. Cancer Prev Res (Phila). 2013;6(5):495-505. PubMed PMID: 23466486.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis. AU - Cheng,Tai-Shan, AU - Chen,Wen-Chi, AU - Lin,Ya-Yun, AU - Tsai,Chin-Hsien, AU - Liao,Chia-I, AU - Shyu,Hsin-Yi, AU - Ko,Chun-Jung, AU - Tzeng,Sheue-Fen, AU - Huang,Chun-Yin, AU - Yang,Pan-Chyr, AU - Hsiao,Pei-Wen, AU - Lee,Ming-Shyue, Y1 - 2013/03/06/ PY - 2013/3/8/entrez PY - 2013/3/8/pubmed PY - 2013/12/20/medline SP - 495 EP - 505 JF - Cancer prevention research (Philadelphia, Pa.) JO - Cancer Prev Res (Phila) VL - 6 IS - 5 N2 - 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. SN - 1940-6215 UR - https://www.unboundmedicine.com/medline/citation/23466486/Curcumin_targeting_pericellular_serine_protease_matriptase_role_in_suppression_of_prostate_cancer_cell_invasion_tumor_growth_and_metastasis_ L2 - http://cancerpreventionresearch.aacrjournals.org/cgi/pmidlookup?view=long&pmid=23466486 DB - PRIME DP - Unbound Medicine ER -