Inhibition of Sanggenon G Isolated from Morus alba on the Metastasis of Cancer Cell
Cancer metastasis is a malignant progression to distant organs by cancer cells. In these processes, the invasive cancer cells must attach on microvessel endothelial cells of other tissues, and degrade to basement membranes and ECM for invasion into other organs/tissues. As part of our ongoing study to search for natural heparinase inhibitors from plants, the stem barks of M. alba were chosen for detail investigation, since the MeOH extract was found to inhibit heparinase at 30 μg/mL. Prenylated flavonoids including sanggenon G have been reported to possess a wide range of pharmacological activities that include anti-inflammatory, antiviral, antimicrobial, antitumor and antiangiogenic effects (Shi et al, 2001; Talla et al, 2003; Kim, et al, 2003). However, this is the first time that sanggenon G is described as a heparinase inhibitor. Because heparinase plays an important role in anticoagulation and cell proliferation, this flavonoid would be expected to be a metastasis inhibitor of cancer cells and also a valuable reagent to explore the mechanism of heparinase/ heparanase-mediated metastasis.
An organic layer prepared from the cortex of Morus alba (Moraceae) was studied in order to identify the active compounds for heparinase.
Bioassay-guided fractionation resulted in the isolation of sanggenon G.
The compound showed inhibitory activity with IC50 of 3.7 μmol/L on heparinase in vitro as well as 24 μmol/L in invasion assay using MDA-MB231 cells. Sanggenon G also had the moderate cytotoxicity at SW 620 (colon) and ACHN (kidney) cancer cell lines with IC50 of 10.96 and 13.44 μmol/L, respectively.
This is the first time that prenylated flavonoid sanggenon G is described as heparinase inhibitor. Besides, this flavonoid would be expected to be a metastasis inhibitor of cancer cells and also a valuable reagent to explore the mechanism of heparinase/heparanase-mediated metastasis.
Key words: cytotoxicity; heparinase/heparanase; Moraceae; Morus alba;
Cui L, Lee H-S, Oh W-K & Ahn J-S. Chinese Herbal Medicines, 2010, 2(4): 23-26
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