Membranous type matrix metalloproteinase 16 induces human prostate cancer metastasis.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, which perform a crucial role in the metastatic spread of cancer. MMP2 and MMP9 are important cancer-associated MMPs in the invasion and metastasis of the majority of carcinomas. As a new member of the membrane-type MMPs, the function of MMP16 associated with invasion and metastasis of cancer remains unclear. In the present study, MMP16 expression in prostate cancer (PCa) tissues and cells was examined, and the high expression of MMP16 was revealed to be associated with advanced prostate tumor stage and PCa cell metastasis. The membrane localization of MMP16 is required for its function. To the best of our knowledge, the present study is the first to demonstrate that MMP16 is associated with advanced prostate tumor stage. As an important mediator of PCa cell metastasis, the membrane localization of MMP16 is required, and MMP16 may be an ideal target candidate for preventing PCa cell metastasis.

Altholactone Inhibits NF-κB and STAT3 Activation and Induces Reactive Oxygen Species-Mediated Apoptosis in Prostate Cancer DU145 Cells.

Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity. Altholactone inhibited proliferation of DU145 cells and induced cell cycle arrest in S phase and triggered apoptosis. Reporter assays revealed that altholactone repressed p65- and TNF-α-enhanced NF-κB transcriptional activity and also inhibited both constitutive and IL-6-induced transcriptional activity of STAT3. Consistent with this, altholactone down-regulated phosphorylation of STAT3 and moreover, decreased constitutively active mutant of STAT3 (STAT3C)-induced transcriptional activity. Altholactone treatment also results in down-regulation of STAT3 target genes such as survivin, and Bcl-2 followed by up regulation of pro-apoptotic Bax protein. However, pre-treatment with the antioxidant N-acetylcysteine (NAC) significantly inhibited the activation of Bax and prevented down-regulation of STAT3 target genes. Collectively, our findings suggest that altholactone induces DU145 cells death through inhibition of NF-κB and STAT3 activity.