Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt/NF-kB/MMP-9 Pathway

Abstract

Hibiscus sabdariffa leaf has been previously shown to possess hypoglycemic, hypolipidemic, and antioxidant effects, and induce tumor cell apoptosis. However, the molecular mechanisms involved in the anticancer activity of H. sabdariffa leaf extract (HLE) are poorly understood. The object of the study was to examine the anti-invasive potential of HLE. First, HLE was demonstrated to be rich in polyphenols. The results of wound-healing assay and in vitro transwell assay revealed that HLE dose-dependently inhibited the migration and invasion of human prostate cancer LNCaP (lymph node carcinoma of the prostate) cells under non-cytotoxic concentrations. Our results further showed that HLE exerted an inhibitory effect on the activity and expressions of matrix metalloproteinase-9 (MMP-9). The HLE-inhibited MMP-9 expression appeared to be a consequence of nuclear factor-kappaB (NF-κB) inactivation because its DNA-binding activity was suppressed by HLE. Molecular data showed all these influences of HLE might be mediated via inhibition of protein kinase B (PKB, also known as Akt)/NF-κB/MMP-9 cascade pathway, as demonstrated by the transfection of Akt1 overexpression vector. Finally, the inhibitory effect of HLE was proven by its inhibition on the growth of LNCaP cells and the expressions of metastasis-related molecular proteins in vivo. These findings suggested that the inhibition of MMP-9 expression by HLE may act through the suppression of the Akt/NF-κB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells.

The significance of Akt/NF-κb signaling pathway in the posterior cataract animal model

“…Akt/NF-kb signaling pathway is a common signal transduction pathway in eukaryotic cells. It is involved in cell polarity, cell division, proliferation and apoptosis, cell adhesion and migration, and so on (12,13). Related studies confi rmed that the inhibition of TGF-beta upstream protein can effectively inhibit the collagen gel contraction induced by TGFand the expression of type I collagen (14,15).…”

Associations of Promoter Methylations and mRNA Expressions of <b><i>MMP-2</i></b>, <b><i>MMP-7</i></b> and <b><i>MMP-9</i></b> with Primary Fallopian Tube Carcinoma

“…Also, correspondingly increased MMPs expression levels were also detected in breast carcinoma, colorectal carcinoma, bladder carcinoma and gastric carcinoma [10,11,18,19,20]. Possible reasons to explain such phenomena are as follows: despite decreasing methylation levels of MMP-2 , MMP-7 and MMP-9 , however, as DNA methylation resulted in gene repression, methylation reduction weakens the recruitment of methyl-CpG-binding domain proteins, leading to less repression on gene expression and indirect increases of gene expression levels [21].…”

Screening of differentially expressed protein kinases in bone marrow endothelial cells and the protective effects of the p38a inhibitor SB203580 on bone marrow in liver fibrosis

“…The central role of protein kinases in regulating cell behavior indicates their potential for use as therapeutic targets in cancer, inflammation and numerous additional diseases, which has been studied widely (17–19). Among the methods used to screen target kinases, whole genome arrays provide a significant amount of information about protein kinases, and have become an important method for identifying and analyzing kinases and kinase families.…”