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Abstract
AimsThough plant metabolic changes are known to occur during interactions with bacteria, these were rarely challenged for pharmacologically active compounds suitable for further drug development. Here, the occurrence of specific chemicals with antiproliferative activity against human cancer cell lines was evidenced in hyperplasia (leafy galls) induced when plants interact with particular phytopathogens, such as the Actinomycete Rhodococcus fascians.MethodsWe examined leafy galls fraction F3.1.1 on cell proliferation, cell division and cytoskeletal disorganization of human cancer cell lines using time-lapse videomicroscopy imaging, combined with flow cytometry and immunofluorescence analysis. We determined the F3.1.1-fraction composition by gas chromatography coupled to mass spectrometry.ResultsThe leafy galls induced on tobacco by R. fascians yielded fraction F3.1.1 which inhibited proliferation of glioblastoma U373 cells with an IC50 of 4.5 µg/mL, F.3.1.1 was shown to increase cell division duration, cause nuclear morphological deformations and cell enlargement, and, at higher concentrations, karyokinesis defects leading to polyploidization and apoptosis. F3.1.1 consisted of a mixture of isomers belonging to the cembrenoids. The cellular defects induced by F3.1.1 were caused by a peculiar cytoskeletal disorganization, with the occurrence of fragmented tubulin and strongly organized microtubule aggregates within the same cell. Colchicine, paclitaxel, and cembrene also affected U373 cell proliferation and karyokinesis, but the induced microtubule rearrangement was very different from that provoked by F3.1.1. Altogether our data indicate that the cembrenoid isomers in F3.1.1 have a unique mode of action and are able to simultaneously modulate microtubule polymerization and stability.
Highlights
Rhodococcus fascians is a phytopathogenic Actinomycete that incites the development of so-called leafy galls (LGs) on a wide range of plant hosts
LG are viewed as the ecological niche of R. fascians [2] and as plant structures where metabolism is modified to contribute to symptom development [1]
LG tissues contain potent compounds that affect the proliferation of different human cancer cell lines
Summary
Rhodococcus fascians is a phytopathogenic Actinomycete that incites the development of so-called leafy galls (LGs) on a wide range of plant hosts. LG formation results from a reprogramming of plant cell fate and plant morphogenesis, leading to the de novo generation of shoot meristems and the activation of existing dormant shoot meristems (for a recent review see Stes et al, 2011). LG are viewed as the ecological niche of R. fascians [2] and as plant structures where metabolism is modified to contribute to symptom development [1]. Phytohormones, mainly cytokinins and auxins, produced by R. fascians are at the basis of symptom induction on the host plants, but the reason for the subsequent developmental blockage is currently unknown. LG can be viewed as chemical interfaces where cell cycle activating and inhibiting compounds are produced
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