The in vivo effect of chelidonine on the stem cell system of planarians

Isolani, Maria Emilia; Pietra, Daniele; Balestrini, Linda; Borghini, Alice; Deri, Paolo; Imbriani, Marcello; Bianucci, Anna Maria Paola; Batistoni, Renata

doi:10.1016/j.ejphar.2012.03.036

Cited by 16 publications

(15 citation statements)

References 27 publications

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“…SYBR Green chemistry-based RT-PCR (GoTaq 2-Step RT-qPCR System, Promega) was carried out on a Rotor-Gene 6000 Real time-PCR (Corbett Research). Real Time RT-PCR was performed at least three times with independent RNA samples, according to the experimental design described by [78]. To analyze gene expression stability, Ct values of two D. japonica reference genes ( D. japonica Elongation factor-2 and D. japonica beta actin ) and three S. mediterranea reference genes ( S. mediterranea Elongation factor-2 , S. mediterranea Glyceraldehyde 3-phosphate dehydrogenase and S. mediterranea ribosomal protein L13 ) were evaluated using Normfinder stability software (Version 0.953).…”

Section: Methodsmentioning

confidence: 99%

Planarians as a Model to Assess In Vivo the Role of Matrix Metalloproteinase Genes during Homeostasis and Regeneration

et al. 2013

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Matrix metalloproteinases (MMPs) are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2) are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB) are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi) during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi). Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues. These results have high potential to generate significant information for development of regenerative and anti cancer therapies.

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Section: Methodsmentioning

confidence: 99%

Planarians as a Model to Assess In Vivo the Role of Matrix Metalloproteinase Genes during Homeostasis and Regeneration

et al. 2013

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“…Chelidonine produces in vivo a significant antiproliferative effect on planarian stem cells in a dose-dependent fashion (Isolani et al, 2012). Chelidonine treatment resulted in mitotic abnormalities and the number of cells able to proceed to anaphase/telophase significantly reduced when compared to the controls.…”

Section: Anticancer Activity: Multiple Mechanismsmentioning

confidence: 97%

Phytochemical and biological research of Chelidonieae pharmaceutical resources

Hao¹,

Gu²,

Xiao³

2015

Medicinal Plants

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“…L. Protopine was found to be cytoprotective against oxidative stress‐induced cell death and has anti‐inflammatory and hepatoprotective effects . Chelidonine was shown to cause mitotic arrest, inhibit tubulin polymerization and possess a significant anti‐proliferative effect . Coptisine, sanguinarine and chelerythrine were reported to have anti‐microbial and anti‐inflammatory activities .…”

Section: Introductionmentioning

confidence: 99%

A sensitive and selective liquid chromatography−tandem mass spectrometry method for simultaneous determination of five isoquinoline alkaloids from Chelidonium majus L. in rat plasma and its application to a pharmacokinetic study

Zhou¹,

Liu²,

Wang³

et al. 2013

J. Mass. Spectrom.

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Chelidonium majus L. is one of the most important medicinal plants of the family Papaveraceae. Its pharmacological effects have been primarily attributed to the presence of a number of alkaloids. In the present study, a sensitive and selective liquid chromatography-tandem mass spectrometry method for simultaneous determination of five isoquinoline alkaloids from Chelidonium majus L. was developed and validated. The analytes (protopine, chelidonine, coptisine, sanguinarine and chelerythrine), together with the internal standard (palmatine), were extracted from acidified rat plasma with ethyl acetate-dichloromethane (4:1, v/v). Chromatographic separation was carried out on a Diamonsil C(18) column with an isocratic mobile phase consisting of acetonitrile and water (adjusted to pH 2.3 with formic acid) (30:70, v/v) at a flow rate of 0.4 ml/min. Mass spectrometric detection was performed by selected reaction monitoring mode via electrospray ionization source operating in positive ionization mode. The assay exhibited good linearity (r ≥ 0.9933) for all the analytes. The lower limits of quantification were 0.197-1.27 ng/ml using only 50 µl of plasma sample. The intra- and inter-day precisions were less than 11.9%, and the accuracy was between -6.3% and 9.3%. The method was successfully applied to the pharmacokinetic study of the five alkaloids in rats after intragastric administration of Chelidonium majus L. extract.

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The in vivo effect of chelidonine on the stem cell system of planarians

Cited by 16 publications

References 27 publications

Planarians as a Model to Assess In Vivo the Role of Matrix Metalloproteinase Genes during Homeostasis and Regeneration

Planarians as a Model to Assess In Vivo the Role of Matrix Metalloproteinase Genes during Homeostasis and Regeneration

Phytochemical and biological research of Chelidonieae pharmaceutical resources

A sensitive and selective liquid chromatography−tandem mass spectrometry method for simultaneous determination of five isoquinoline alkaloids from Chelidonium majus L. in rat plasma and its application to a pharmacokinetic study

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