title: Cytotoxic and apoptotic effects of leptocarpin, a plant-derived sesquiterpene lactone, on human cancer cell lines.
abstract: Sesquiterpene lactones have attracted much attention in drug research because they present a series of biological activities such as anticancer, antifungal, anti-inflammatory, antimicrobial and antioxidant. Leptocarpin (LTC) is a sesquiterpene lactone isolated from a native Chilean plant, Leptocarpha rivularis, which has been widely used in traditional medicine by Mapuche people. Previous work has demonstrated that LTC decreases cell viability of cancer cell lines. In this contribution, we analyze the mechanism of LTC cytotoxicity on different cancer cell lines. The results show that in all cases LTC induces an apoptotic process and inhibition of NF-κB. Apoptosis has been confirmed by observing condensation of chromatin, nuclear fragmentation, release of cytochrome c into the cytosol, and increasing of caspase-3 activity. It has also been found that LTC is an effective inhibitor of NF-κB, which suggests that leptocarpin-induced cytotoxicity involves in some degree the inhibition of NF-κB signaling pathway. The concentration at which LTC inhibits NF-κB activity to the control level is similar or even lower than that found for parthenolide and others sesquiterpene lactones. These results indicate that leptocarpine is a very interesting molecule that could be considered as therapeutic agent for cancer treatment.
authors.affiliation: Departamento de Química, Facultad de Ciencias Exactas, Universidad Andrés Bello, Quillota 910, Viña del Mar, 2520000, Chile. Electronic address: samybrs@hotmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bosio
authors.affiliation: Departamento de Química, Facultad de Ciencias Exactas, Universidad Andrés Bello, Quillota 910, Viña del Mar, 2520000, Chile. Electronic address: volgin_4@hotmail.com.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Tomasoni
authors.affiliation: Departamento de Química, Facultad de Ciencias Exactas, Universidad Andrés Bello, Quillota 910, Viña del Mar, 2520000, Chile. Electronic address: rmartinez@unab.cl.
authors.forename: Rolando
authors.initials: R
authors.lastname: Martínez
authors.affiliation: Instituto de Ciencias Químicas Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile, Llano Subercaseaux 2801, San Miguel, Santiago, Chile. Electronic address: andres.olea@uautonoma.cl.
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Olea
authors.affiliation: Instituto de Ciencias Químicas Aplicadas, Facultad de Ingeniería, Universidad Autónoma de Chile, Llano Subercaseaux 2801, San Miguel, Santiago, Chile. Electronic address: hector.carrasco@uautonoma.cl.
authors.forename: Héctor
authors.initials: H
authors.lastname: Carrasco
authors.affiliation: Centro de Investigaciones Biomédicas (CIB), Escuela de Medicina, Universidad de Valparaíso, Av. Hontaneda 2664, Valparaíso, 234000, Chile. Electronic address: juan.villena@uv.cl.
authors.forename: Joan
authors.initials: J
authors.lastname: Villena
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae / Q000737:chemistry*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C093534:leptocarpin; D045304:Cytochromes c
keywords: Apoptosis; Cancer cell lines; Cytotoxicity; Factor NF-κB; Leptocarpin; Sesquiterpene lactones