Zanthoxylum avicennae extracts inhibit cell proliferation through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells in vitro and in vivo

• Published in: International journal of molecular medicine Vol. 29; no. 6; pp. 1045 - 1052
• Main Authors: Dung, Tran, Chang, Hsien-Cheh, Binh, Truong, Lee, Maw-Rong, Tsai, Chang-Hai, Tsai, Fuu-Jen, Kuo, Wei-Wen, Chen, Li-Mien, Huang, Chih-Yang
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-06-2012
• Subjects: Animals; Blotting, Western; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - enzymology; Carcinoma, Hepatocellular - pathology; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Down-Regulation - drug effects; Enzyme Activation - drug effects; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - enzymology; Liver Neoplasms - pathology; Male; Mice; Mice, Nude; Models, Biological; Okadaic Acid - pharmacology; Phosphorylation - drug effects; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Protein Phosphatase 2 - metabolism; Proto-Oncogene Proteins c-akt - metabolism; RNA, Small Interfering - metabolism; Xenograft Model Antitumor Assays; Zanthoxylum - chemistry
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2012.938

Hepatocellular carcinoma is a common type of cancer that is usually associated
with poor prognosis. In this study, we examined the in vitro and in vivo mechanisms
of the traditional Vietnamese herb Zanthoxylum avicennae on the inhibition of
HA22T human hepatocellular carcinoma cell proliferation. HA22T cells were treated
with different concentrations of Zanthoxylum avicennae extracts (YBBEs) and analyzed
with the MTT assay, western blot analysis, flow cytometry, siRNA transfection
assays and co-immunoprecipitation assay. Additionally, the HA22T-implanted xenograft
nude mouse model was applied to confirm the cellular effects. YBBEs showed a strong
inhibition of HA22T cell viability in a dose-dependent manner and significantly
reduced cell proliferation-related proteins as well as induced cell cycle arrest
in the G2/M phase. Protein phosphatase 2A (PP2A) siRNA or okadaic acid totally
blocked YBBE-mediated cell proliferation inhibition. In addition, an HA22T-implanted
nude mouse model further confirmed that YBBEs inhibit HA22T tumor cell growth
and downregulate the survival and cell cycle regulating proteins, as well as activate
the PP2A protein. Our findings indicate that the inhibition of HA22T cell proliferation
by YBBEs is mediated through PP2A activation.