Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest Shwu-Bin Lin a,b, * , Chyi-Hann Li a , Shiuh-Sheng Lee c , Lou-Sing Kan d a Graduate Institute of Medical Technology, College of Medicine, National Taiwan University, Taipei, 10016, Taiwan, ROC b Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan, ROC c Graduate Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan, ROC d Institute of Chemistry, Academia Sinica, Taipei, Taiwan, ROC Received 15 July 2002; accepted 15 November 2002 Abstract The medicinal mushroom Ganoderma lucidum (G. lucidum) has been used in the Orient for the prevention and treatment of various diseases including cancer. Except for the immune enhancing properties of its polysaccharide constituent, very little is known about the anticancer activity of another major constituent, triterpenes. In this report, we studied the anticancer mechanism of triterpene-enriched extracts from G. lucidum. The triterpene- enriched fraction, WEES-G6, was prepared from mycelia of G. lucidum by sequential hot water extraction, removal of ethanol-insoluble polysaccharides and then gel-filtration chromatography. We found that WEES-G6 inhibited growth of human hepatoma Huh-7 cells, but not Chang liver cells, a normal human liver cell line. Treatment with WEES-G6 caused a rapid decrease in the activity of cell growth regulative protein, PKC, and the activation of JNK and p38 MAP kinases. The changes in these molecules resulted in a prolonged G2 cell cycle phase and strong growth inhibition. None of these effects were seen in the normal liver cells. Our findings suggest that the triterpenes contained in G. lucidum are potential anticancer agents. D 2003 Elsevier Science Inc. All rights reserved. Keywords: G. lucidum; Triterpenes; Tumorcidal; PKC; MAP kinases 0024-3205/03/$ - see front matter D 2003 Elsevier Science Inc. All rights reserved. doi:10.1016/S0024-3205(03)00124-3 * Corresponding author. Graduate Institute of Medical Technology, College of Medicine, National Taiwan University, No. 1 Chang-Te St., Taipei, 10016, Taiwan, ROC. Fax: +886-2-2371-1574. E-mail address: sblin@ha.mc.ntu.edu.tw (S.-B. Lin). www.elsevier.com/locate/lifescie Life Sciences 72 (2003) 2381 – 2390