柳杉粗萃物及其生物活性化合物terpinen-4-ol 對肺癌之抗癌功能研究

Abstract

Lung cancer is one of the most malignant cancer among the men and women. There are two main types of lung cancer: Small Cell Lung Cancers (SCLC) and Non-Small Cell Lung Cancers (NSCLC). Non-small cell lung cancers represent more than 80 percent of lung cancers in Taiwan. The report shows that a novel abietane diterpene, 6-hydroxy-5, 6-dehydrosugiol (HDHS), isolated from the stem bark of Cryptomeria japonica, was a potent AR antagonist in PCa cells. HDHS was found to be antiproliferative and proapoptotic against an ablation-resistant 22Rv1 tumor still expressing AR and responsive to androgen. This study was designed to exploit the molecular mechanisms of the extract of Cryptomeria japonica leaves and Cryptomeria japonica bioactive compound terpinen-4-ol induce apoptosis in lung cancer. From preliminary research and screening, the extract of Cryptomeria japonica leaves had inhibitory effect on lung cancer cells proliferation. The results indicated that the extract of Cryptomeria japonica leaves and terpinen-4-ol inhibited the cell viability of lung cancer cells by inducing apoptosis and increasing in the sub-G1 cell population. In addition, the extract of Cryptomeria japonica leaves and terpinen-4-ol also induced apoptosis in lung cancer cells, as determined by Annexin V staining assay. DNA fragmentation assay showed that the extract of Cryptomeria japonica leaves induced apoptosis. The extract of Cryptomeria japonica leaves and terpinen-4-ol increased the expression of pro-apoptosis Bax, but decreased the expression of anti-apoptosis Bcl-2 and subsequently triggered the mitochondrial apoptotic pathway (release cytochrome c and activation of caspase-9 and caspase-3). Taken together, these findings suggest that the crude extract of the leaves of Cryptomeria japonica and terpinen-4-ol can exhibit antitumor activity via caspase activation and MAPK regulation and can be effectively applied to cancer as a cancer chemopreventive agent.