Cytotoxic Effect of the Diterpene Lactone Dehydrocrotonin from Croton cajucara on Human Promyelocytic Leukemia Cells

Abstract 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 IC 50 of 500 μM; mitochondrial function (MTT reduction), was also inhibited (IC 50 = 300 μM), 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 (IC 50 = 180 μM) and protein content (IC 50 = 150 μM). The flavonoid utilized as positive control myricetin and the following IC 50 values were obtained after 24 h of treatment: 300 and 192 μM 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.