The effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways

Panzer, Annie; Joubert, Annie M.; Bianchi, Pepita; Hamel, Ernest; Seegers, J.C.

doi:10.1078/0171-9335-00135

Cited by 54 publications

(33 citation statements)

References 28 publications

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“…The proposed mechanism of the chelidonine effect is similar to the action of well known anti-cancer alkaloid vinblastine [7]. It was determined that chelidonine affected tubulin polymerization and blocked cell cycle in the mitotic phase [18]. In our studies, we observed an increase in number of cells with an altered (loosed) chromatin (data not presented).…”

Section: Discussionsupporting

confidence: 59%

“…The mechanisms of biological action of specific alkaloids are still poorly understood. Chelidonine was shown to interact with tubulin in target cells and cause their mitotic arrest [18]. The molecules of chelerythrine, sanguinarine, berberine and coptisine possess a positive charge due to the presence of quaternary nitrogen, and exhibit a significant inhibitory effect on the mitochondrial respiration [2].…”

Section: Introductionmentioning

confidence: 99%

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Correlation of the cytotoxic activity of four different alkaloids, from Chelidonium majus (greater celandine), with their DNA intercalating properties and ability to induce breaks in the DNA of NK/Ly murine lymphoma cells

Kaminskyy¹,

Lootsik

Stoika³

2006

Open Life Sciences

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Abstract:The purpose of this study was to examine the relationship between the DNA intercalating characteristics and the DNA damaging capacity of four alkaloids extracted from Chelidonium majus L, as well as their toxicity towards murine NK/Ly lymphoma cells. Chelerythrine, sanguinarine and coptisine were found to be intercalated into the DNA isolated from NK/Ly cells, meanwhile, chelidonine exhibited no affinity to DNA. Sanguinarine exhibited the greatest toxicity toward NK/Ly cells, and the toxicity of the other three decreased in descending order: chelerythrine, coptisine and chelidonine. Chelerythrine and sanguinarine caused DNA damage, illustrated by the formation of comets of the third class. Coptisine was less toxic than chelerythrine and sanguinarine, and affected the formation the same class of comets in higher concentration. The quantity of comets induced by chelidonine were negligible, a finding consistent with its inability to intercalate into DNA structure. The ability of four main alkaloids of Chelidonium majus L., to intercalate into DNA isolated from murine NK/Ly lymphoma cells, correlated with their ability to induce breaks in cellular DNA and with their toxic effect towards those cells.

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Correlation of the cytotoxic activity of four different alkaloids, from Chelidonium majus (greater celandine), with their DNA intercalating properties and ability to induce breaks in the DNA of NK/Ly murine lymphoma cells

Kaminskyy¹,

Lootsik

Stoika³

2006

Open Life Sciences

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“…4 Panzer et al found that Ukrain inhibits tubulin polymerization, leading to impaired microtubule dynamics, resulting in activation of the spindle checkpoint and thus a metaphase block. 5 In addition, Ukrain has been found to decrease the synthesis of DNA, RNA and proteins, 6 and to inhibit cellular oxygen consumption. 7 Ukrain can induce apoptosis in cancer cells in vitro 4,8,9 and in vivo 10 by a mechanism independent of changes in bcl-2 or bax expression.…”

Section: Introductionmentioning

confidence: 99%

NF-κB does not influence the induction of apoptosis by Ukrain

Mendoza

Zamora²,

Gallardo³

et al. 2006

Cancer Biology & Therapy

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“…It was previously shown that UK decreased cell proliferation and increased the blocking of cells in G2/M because of the depolymerization of tubulin [23] and the (b) Bar graphs showing proMMP-2 and proMMP-9 activity in Caki-1, Caki-2, and ACHN serum-free conditioned media after densitometric analysis of lytic bands following SDS-zymography. Our results show that Ukrain significantly affects MMP-2 and MMP-9 activity, suggesting that this drug may elicit a relevant effect on the mechanisms responsible for tumor invasion.…”

Section: Discussionmentioning

confidence: 99%

Malignant phenotype of renal cell carcinoma cells is switched by Ukrain administration in vitro

Gagliano¹,

Pettinari²,

Aureli³

et al. 2011

Anti-Cancer Drugs

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aWe investigated whether Ukrain modulates the malignant phenotype of clear cell renal cell carcinoma (ccRCC) cells Caki-1, Caki-2, and ACHN treated with four doses (5, 10, 20, and 40 lmol/l) for 24 and 48 h. The epithelial-tomesenchymal transition markers E-cadherin, b-catenin, and vimentin were analyzed by immunofluorescence as well as actin and tubulin; matrix metalloproteinase-2 and matrix metalloproteinase-9 activity was analyzed by SDS-zymography, intracellular and secreted SPARC levels by western blot, and cell cycle by flow cytometry. Ukrain did not induce E-cadherin/b-catenin immunoreactivity at the cell-cell boundary, although it determined the actin cortical expression in Caki-2 and ACHN, and did not affect vimentin organization; however, in some Caki-1 and ACHN cells the perinuclear concentration of vimentin was consistent with its downregulation. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activity was significantly downregulated 48 h after 20 lmol/l Ukrain administration. At this time point, Ukrain significantly decreased migration and invasion, and downregulated SPARC levels in cell supernatants at all doses in Caki-2, and at 20 lmol/l in Caki-1 and ACHN cells. Concomitantly, SPARC was upregulated in all ccRCC cells, suggesting that Ukrain could also affect cell proliferation by cell cycle inhibition, as supported by the cell cycle analysis, as SPARC also acts as a cell cycle inhibitor. Our results suggest that Ukrain may switch the epithelial-to-mesenchymal transition-related phenotype of ccRCC cells, and targets the two major aspects involved in RCC progression, such as tumor invasion/microenvironment remodeling and cell proliferation.

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The effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways

Cited by 54 publications

References 28 publications

Correlation of the cytotoxic activity of four different alkaloids, from Chelidonium majus (greater celandine), with their DNA intercalating properties and ability to induce breaks in the DNA of NK/Ly murine lymphoma cells

Correlation of the cytotoxic activity of four different alkaloids, from Chelidonium majus (greater celandine), with their DNA intercalating properties and ability to induce breaks in the DNA of NK/Ly murine lymphoma cells

NF-κB does not influence the induction of apoptosis by Ukrain

Malignant phenotype of renal cell carcinoma cells is switched by Ukrain administration in vitro

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