title: The epimer of kaurenoic acid from Croton antisyphiliticus is cytotoxic toward B-16 and HeLa tumor cells through apoptosis induction.
abstract: Cancer has become the leading cause of death in developing countries due to increased life expectancy of the population and changes in lifestyle. Studies on active principles of plant have motivated researchers to develop new antitumor agents that are specific and effective for treatment of neoplasms. Kaurane diterpenes are considered important compounds in the development of new and highly effective anticancer chemotherapeutic agents due to their cytotoxic properties in the induction of apoptosis. We evaluated the cytotoxic and apoptotic activity of the epimer of kaurenoic acid (EKA) isolated from the medicinal plant Croton antisyphiliticus (Euphorbiaceae) toward tumor cell lines HeLa and B-16 and normal fibroblasts 3T3. Based on analyses with the MTT test, EKA showed cytotoxic activity, with half maximal inhibitory concentration values of 59.41, 68.18 and 60.30 µg/mL for the B-16, HeLa and 3T3 cell lines, respectively. The assay for necrotic or apoptotic cells by differential staining showed induction of apoptosis in all three cell lines. We conclude that EKA is not selective between tumor and normal cell lines; the mechanism of action of EKA is induction of apoptosis, which is part of the innate mechanism of cell defense against neoplasia.
authors.affiliation: Unidade de Biotecnologia, Universidade de Ribeirão Preto, Ribeirão Preto, SP, Brasil.
authors.forename: V C
authors.initials: VC
authors.lastname: Fernandes
authors.forename: S I V
authors.initials: SI
authors.lastname: Pereira
authors.forename: J
authors.initials: J
authors.lastname: Coppede
authors.forename: J S
authors.initials: JS
authors.lastname: Martins
authors.forename: W F
authors.initials: WF
authors.lastname: Rizo
authors.forename: R O
authors.initials: RO
authors.lastname: Beleboni
authors.forename: M
authors.initials: M
authors.lastname: Marins
authors.forename: P S
authors.initials: PS
authors.lastname: Pereira
authors.forename: A M S
authors.initials: AM
authors.lastname: Pereira
authors.forename: A L
authors.initials: AL
authors.lastname: Fachin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D029802:Croton / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008546:Melanoma, Experimental; D051379:Mice; D041681:NIH 3T3 Cells; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D010936:Plant Extracts; C051436:kaurenoic acid