Cytotoxic effect of the diterpene lactone dehydrocrotonin from Croton cajucara on human promyelocytic leukemia cells

Diterpenes exhibit potent antineoplastic properties against human and murine carcinoma cell lines. trans-Dehydrocrotonin from Croton cajucara, a Brazilian medicinal plant, is a nor-diterpene with antiulcerogenic activity. In this work, we examined the effect of trans-dehydrocrotonin (t-DCTN) on the vitality of HL60 cells by assessing the MTT reduction, protein content and phosphatase activity of these cells. Protein quantification indicated that t-DCTN reduced the number of cells with an IC50 of 500 muM; mitochondrial function (MTT reduction), was also inhibited (IC50 = 300 MM), when the cells were treated for 24 h. In contrast, when the cells were treated with this lactone in the initial plating and cultured for 96 h, t-DCTN was more toxic for all parameters analyzed: MTT and phosphatase activity (IC50 = 180 muM) and protein content (IC50 = 150 muM). The flavonoid utilized as positive control myricetin and the following IC50 values were obtained after 24 h of treatment: 300 and 192 muM for protein content and MTT reduction, respectively. According to the chemical characteristics of both compounds, the cytotoxic effect of t-DCTN could be explained through two mechanisms: adduct formation with DNA and proteins and/or oxidative stress induction.