title: The cytotoxic and embryotoxic effects of kaurenoic acid, a diterpene isolated from Copaifera langsdorffii oleo-resin.
abstract: In this work, we studied the effects of kaurenoic acid, a diterpene isolated from the oleo-resin of Copaifera langsdorffii in developing sea urchin (Lytechinus variegatus) embryos, on tumor cell growth in microculture tetrazolium (MTT) test and on mouse and human erythrocytes in hemolysis assay. Continuous exposure of embryos to kaurenoic acid starting immediately after fertilization inhibited the first cleavage (IC(50): 84.2 microM) and progressively induced embryo destruction (IC(50): 44.7 microM and < 10 microM for blastulae and larvae stages, respectively). In MTT assay, kaurenoic acid at a concentration of 78 microM produced growth inhibition of CEM leukemic cells by 95%, MCF-7 breast and HCT-8 colon cancer cells by 45% each. Further, kaurenoic acid induced a dose-dependent hemolysis of mouse and human erythrocytes with an EC(50) of 74.0 and 56.4 microM, respectively. The destruction of sea urchin embryos, the inhibition of tumor cell growth and the hemolysis of mouse and human erythrocytes indicate the potential cytotoxicity of kaurenoic acid.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Cel Nunes de Melo, 1127, P.O. Box 3157, 60430-270, Fortaleza, CE, Brazil.
authors.forename: L V
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: G M A
authors.initials: GM
authors.lastname: Cunha
authors.forename: P A M
authors.initials: PA
authors.lastname: Farias
authors.forename: G S B
authors.initials: GS
authors.lastname: Viana
authors.forename: K M A
authors.initials: KM
authors.lastname: Cunha
authors.forename: C
authors.initials: C
authors.lastname: Pessoa
authors.forename: M O
authors.initials: MO
authors.lastname: Moraes
authors.forename: E R
authors.initials: ER
authors.lastname: Silveira
authors.forename: N V
authors.initials: NV
authors.lastname: Gramosa
authors.forename: V S N
authors.initials: VS
authors.lastname: Rao
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry / Q000633:toxicity*; D004224:Diterpenes / Q000737:chemistry / Q000633:toxicity*; D004625:Embryo, Nonmammalian; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010946:Plants, Medicinal / Q000737:chemistry*; D012116:Resins, Plant / Q000737:chemistry*; D012617:Sea Urchins / Q000502:physiology*; D013723:Teratogens / Q000737:chemistry / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D003603:Cytotoxins; D004224:Diterpenes; D012116:Resins, Plant; D013723:Teratogens; C051436:kaurenoic acid