eCAM Advance Access published online on September 29, 2009
eCAM, doi:10.1093/ecam/nep142
Alpinia pricei Rhizome Extracts Induce Cell Cycle Arrest in Human Squamous Carcinoma KB Cells and Suppress Tumor Growth in Nude Mice
1Department of Cosmeceutics, College of Pharmacy, 2Institute of Nutrition, China Medical University and 3Department of Forestry, National Chung Hsing University, Taichung 40402, Taiwan
Alpinia pricei has been shown to induce apoptosis in human squamous carcinoma (KB) cells. In this study, we report the effectiveness of the ethanol (70%) extracts of A. pricei rhizome (AP extracts) in terms of tumor regression as determined using both in vitro cell culture and in vivo athymic nude mice models of KB cells. We found that the AP extract (25–200 µg/ml) treatment decreased the proliferation of KB cells by arresting progression through the G2/M phase of the cell cycle. This cell cycle blockade was associated with reductions in cyclin A and B1, Cdc2, and Cdc25C, and increased p21/WAF1, Wee1, p53 and phospho-p53 (p-p53) in a dose- and time-dependent manner. Moreover, we found that AP extract treatment decreased metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (u-PA) expression, while expression of their endogenous inhibitors, tissue inhibitor of MMP-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1), were increased in KB cells. Furthermore, AP extract treatment effectively delayed tumor incidence in nude mice inoculated with KB cells and reduced the tumor burden. AP extract treatment also induced apoptotic DNA fragmentation, as detected by in situ TUNEL staining. Thus, A. pricei may possess antitumor activity in human squamous carcinoma (KB) cells.
Keywords: KB cells – nude mice – apoptosis – antitumor
For reprints and all correspondence: You-Cheng Hseu, Department of Cosmeceutics, College of Pharmacy, China Medical University, 91 Huseh-Shih Road, Taichung 40402, Taiwan. Tel: +886-4-22053366, ext. 5308; Fax: +886-4-22078083; E-mail: ychseu{at}mail.cmu.edu.tw
Received January 21, 2009; accepted August 30, 2009