title: 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-kB/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-kB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells.
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan. nydrskin@yahoo.com.tw.
authors.forename: Chun-Tang
authors.initials: CT
authors.lastname: Chiu
authors.affiliation: School of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan. cjh0828@csmu.edu.tw.
authors.forename: Jing-Hsien
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan. fpchou@csmu.edu.tw.
authors.forename: Fen-Pi
authors.initials: FP
authors.lastname: Chou
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan. linhh@csmu.edu.tw.|Department of Clinical Laboratory, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung City 40201, Taiwan. linhh@csmu.edu.tw.
authors.forename: Hui-Hsuan
authors.initials: HH
authors.lastname: Lin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D031584:Hibiscus / Q000737:chemistry*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9
keywords: Akt/NF-kB/MMP-9 cascade pathway; Hibiscus sabdariffa leaf; human prostate cancer; metastasis; polyphenols