Cytotoxicity of demalonyl thyrsiflorin A, a semisynthetic labdane-derived diterpenoid, to melanoma cells

Diterpenes are compounds with complex structure and due to their unique carbon skeleton and interesting biological activities, have been the focus of continuous studies for the development of new anticancer agents. The plants of the genus Calceolaria (Scrophulariaceae family), native of South America have also yielded several new diterpenes with the scopadulane skeleton, such as thyrsiflorin A. The present study was undertaken to investigate the effect of the semisynthetic compound, demalonyl thyrsiflorin A on human melanoma cells. In A375 cells compound demalonyl thyrsiflorin A showed a clear dose-response relationship in the range of 6.25-50μM concentrations. In addition, we demonstrated an apoptotic response after treatment of cancer cells with this semisynthetic phenolic labdane diterpene at 6.25 and 12.5μM concentrations that probably involves the reduction of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of the caspase cascade at higher concentrations, 25 and 50μM, correlated with additional reactive oxygen species increase, probably switched the mode of demalonyl thyrsiflorin A-induced cell death from apoptosis to necrosis