β-Thujaplicin Zinc Chelate Induces Apoptosis in Mouse High Metastatic Melanoma B16BL6 Cells

The cytotoxic effects of β-thujaplicin and five kinds of metal chelates were examined on mouse melanoma B16BL6 cells by cell viability and lactate dehydrogenase (LDH) release assay. β-Thujaplicin-zinc chalate and β-thujaplicin-copper chelate had higher cytotoxic effects than β-thujaplicin, and the 50% effective does (ED50) of these metal chelates were 12.5 and 25 μM, respectively. In addition, the zinc chelate induced DNA ladder formation in B16BL6 cells, as shown by the DNA fragmentation assay, suggesting that cell death induced by the zinc chelate is apoptosis. The zinc chelate also had a cytotoxic effect and induced DNA fragmentation on other tumor cell lines : HeLa, Meth A, and B16F1 cells, but not on normal human diploid fibroblasts FS-4. These results suggest that β-thujaplicin-zinc chelate induces apoptotic cell death in various tumor cell lines and is a potent antitumor agent for tumor cells including malignant melanomas.