Alpinia priceiRhizome Extracts Induce Cell Cycle Arrest in Human Squamous Carcinoma KB Cells and Suppress Tumor Growth in Nude Mice

Abstract

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.