title: 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 IC50 of 500 microM; mitochondrial function (MTT reduction), was also inhibited (IC50 = 300 microM), 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 microM) and protein content (IC50 = 150 microM). The flavonoid utilized as positive control myricetin and the following IC50 values were obtained after 24 h of treatment: 300 and 192 microM 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.
authors.forename: Ana Claudia Galvão
authors.initials: AC
authors.lastname: Freire
authors.forename: Patrícia
authors.initials: P
authors.lastname: da Silva Melo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
authors.forename: Marcela
authors.initials: M
authors.lastname: Haun
authors.forename: Nelson
authors.initials: N
authors.lastname: Durán
authors.forename: Carmen Veríssima
authors.initials: CV
authors.lastname: Ferreira
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D029802:Croton / Q000737:chemistry*; D004224:Diterpenes / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D010946:Plants, Medicinal; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D013778:Tetrazolium Salts; D013844:Thiazoles; C103060:dehydrocrotonin; C022616:thiazolyl blue