Sesquiterpene lactones from Ambrosia spp. are active against a murine lymphoma cell line by inducing apoptosis and cell cycle arrest

MARTINO RENZO; BEER FLORENCIA; ELSO ORLANDO; DONADEL OSVALDO; SÜLSEN VALERIA; ANESINI CLAUDIA

TOXICOLOGY IN VITRO : AN INTERNATIONAL JOURNAL PUBLISHED IN ASSOCIATION WITH BIBRA.

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2015 vol. 29 p. 1529 - 1536

0887-2333

Sesquiterpene lactones(STLs) are natural terpenoid compounds. They have been recognized as antitumoragents. The purpose of this investigation was to explore the antiproliferativeeffects of psilostachyin, psilostachyin C, peruvin and cumanin onthe murine lymphoma cell line BW5147.Cells were treated with the STLs at different concentrations. Tritiatedthymidine uptake was employed to determine cell proliferation. MTT assay wasused to analyze cell viability. Flow cytometry assay with annexin V-FITC andpropidium iodide was employed to evaluate cell death. Reactive oxygen species(ROS), mitochondrial membrane potential and cell cycle analysis were alsoevaluated by flow cytometry. Antioxidant enzymes activities were determinedspectrophotometrically by kinetic assays.Results showed that these STLs inhibited cell proliferation in aconcentration-dependent manner by exerting cytotoxicity through apoptosis.Psilostachyin C was the most active and the less toxic compound. This STLinduced apoptosis with an impairment in mitochondrial membrane potential. Psilostachyin C was able toinduce ROS generation, related to a modulation of the antioxidant enzymesactivity. In addition, it induced cell cycle arrest in S phase. In conclusion,psilostachyin C was found to be active against lymphoma cells exerting bothcytostatic and cytotoxic effects. These findings may provide a novel approachfor lymphoma treatment.