Secondary metabolites from Excoecaria formosana and their anti-hepatocellular carcinoma activity

Glycine N-methyltransferase (GNMT) is a tumor suppressor gene for hepatocellular carcinoma (HCC). The agents that enhance the expression of GNMT would have a beneficial effect on liver and utility in anticancer therapies. Previous studies also proved that GNMT might improve the antitumor activity of standard chemotherapeutic drugs, and expression of GNMT is highly downregulated in the livers of patients at risk of developing HCC such as those with hepatitis C virus and alcohol-induced cirrhosis. So GNMT could be an excellent target in drug screening for anti-HCC medicine.

Approximately 1,400 species of Formosan indigenous plants have been screened for the GNMT promoter activity, and Excoecaria formosana (Hay.) Hay. (Euphorbiaceae) is the most potential species. E. formosana is a shrub and mainly distributed in Tonkin, Indo-China, the southern part of Taiwan in thickets and forests along the seashores. Till now, no investigation of chemical constituents and bioactivity from E. formosana have been reported, so it is potential for research.

Previously, we reported one new steroid: 6'-(stigmast-5-en-7-hydroperoxy-3-O-β-glucopyransidyl)hexadecanoate (1) and thirteen known compounds including four steroids, three benzenoids, a mixture of cerebrosides, one coumarin, and one diterpene from the active ethyl acetate-soluble layer of this plant. Continuing investigation led to the isolation of one new coumarinolignan: excocoumarin A (2), one new diterpene: excoterpenol A (3) and twenty-one known compounds, including one apocarotenoid, three benzenoids, one coumarin, six coumarinolignans, two diterpenes, one flavonoid, two steroids and five tannins. The structures of these new compounds (1–3) were elucidated by 1D, 2D NMR, UV, IR, ESIMS, and HRESIMS analysis. The GNMT promoter activity of these constituents have been evaluated, and the isolation of the active subfractions of this plant is still in progress.