Department of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, R817, 8F, No. 1, Section 1, Jen-Ai Rd., Taipei, Taiwan.
Cancer Prev Res (Phila). 2013 May;6(5):495-505. doi: 10.1158/1940-6207.CAPR-12-0293-T. Epub 2013 Mar 6.
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.
姜黄素已被证明对前列腺癌具有有效的化学预防和抗肿瘤作用。然而，姜黄素抑制前列腺癌细胞侵袭、肿瘤生长和转移的能力的分子机制尚不清楚。在这项研究中，我们已经表明，姜黄素可以抑制表皮生长因子（EGF）刺激和人表皮生长因子（HER）刺激的 PC-3 细胞侵袭，以及雄激素诱导的 LNCaP 细胞侵袭。姜黄素处理显著导致基质金属蛋白酶 9 活性降低和细胞组织蛋白酶下调，组织蛋白酶是一种膜锚定丝氨酸蛋白酶，在肿瘤形成和侵袭中具有致癌作用。我们的数据进一步表明，姜黄素能够抑制雄激素和 EGF 对组织蛋白酶激活的诱导作用，并降低其过表达后的激活水平，这表明姜黄素可能通过阻断不同的信号通路来抑制蛋白酶。此外，姜黄素通过促进组织蛋白酶进入细胞外环境而减少细胞中激活的组织蛋白酶，而不是通过改变组织蛋白酶基因表达。此外，姜黄素显著抑制了由组织蛋白酶过表达诱导的前列腺癌细胞的侵袭能力。在异种移植模型中，姜黄素不仅抑制前列腺癌肿瘤的生长和转移，而且还下调体内组织蛋白酶的活性。总的来说，数据表明姜黄素对前列腺癌细胞侵袭、肿瘤生长和转移具有抑制作用，至少部分是通过下调组织蛋白酶的功能。
