Purification of the Alkaloid Lycorine and Simultaneous Analysis of Ascorbic Acid and Lycorine by Micellar Electrokinetic Capillary Chromatography

Davey, Mark W.; Persiau, Geert; Bruyn, André De; Damme, Josef Van; Bauw, Guy; Montagu, Marc Van

doi:10.1006/abio.1997.2544

Cited by 17 publications

(10 citation statements)

References 40 publications

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“…Nonetheless, the possibility that lycorine exerts its effects via mitochondrial mechanisms is supported by studies in Saccharomyces cerevisiae, which have demonstrated that cells lacking mitochondrial DNA are resistant to lycorine. 50 Elderly CLL patients are commonly excluded from clinical trials because of their susceptibility to the development of cytopenia and infections and in younger patients there is an inevitable development of chemoresistance to conventional agents. Thus more targeted therapies are urgently required.…”

Section: Discussionmentioning

confidence: 99%

Lycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate- and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reported CD40-mediated drug resistance

Hayden¹,

Pratt²,

Drayson³

et al. 2010

Haematologica

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BackgroundTumor cells in chronic lymphocytic leukemia accumulate in the periphery through the proliferation of a minority of cells in lymph nodes. The proliferative and survival signals in these proliferation centers include interactions with T lymphocytes expressing CD40 ligand. We have demonstrated that the low toxicity combination of bezafibrate and medroxyprogesterone acetate induces mitochondrial superoxide-mediated apoptosis of non-CD40-liganded cells but not of cells exposed to CD40 ligand. Here, we assessed the ability of dasatinib and lycorine to restore bezafibrate-and medroxyprogesterone acetate-induced apoptosis in cells exposed to CD40 ligand. In parallel experiments we compared the ability of dasatinib to induce apoptosis of cells co-treated with fludarabine. Design and MethodsPrimary chronic lymphocytic leukemia and peripheral blood mononuclear cells were exposed to drug combinations for 72 hours on control and CD40 ligand-expressing fibroblast monolayers. Cells were harvested and analyzed for apoptosis and levels of mitochondrial superoxide using flow cytometry. In some experiments cells were removed from CD40 ligand at 48 hours, retreated and analyzed after a further 24 hours. The effect of CD40 ligand and drug treatments on mitochondrial superoxide levels were assessed. ResultsAs previously described, dasatinib rendered cells sensitive to fludarabine but only when CD40 ligand was removed for the last 24 hours of culture. In contrast, lycorine restored the bezafibrate-and medroxyprogesterone acetate-induced apoptosis associated with mitochondrial superoxide even during continuous exposure to CD40 ligand. Furthermore, combined bezafibrate, medroxyprogesterone acetate and lycorine had little effect against normal peripheral blood mononuclear cells, whereas dasatinib with fludarabine induced high levels of apoptosis. ConclusionsOur data indicate the potential of bezafibrate, medroxyprogesterone acetate and lycorine as novel therapy in chronic lymphocytic leukemia and have important implications for the reported potential of c-abl kinase inhibitors in this disease.Key words: bezafibrate, medroxyprogesterone acetate, lycorine, chronic lymphocytic leukemia, mitochondrial superoxide, CD40 ligand. CD40-mediated drug resistance. Haematologica 2010;95(11):1889-1896. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Hayden RE, Pratt G, Drayson MT, and Bunce CM. Lycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate-and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reportedLycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate-and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reported CD40-mediated drug resistance

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Section: Discussionmentioning

confidence: 99%

Lycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate- and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reported CD40-mediated drug resistance

Hayden¹,

Pratt²,

Drayson³

et al. 2010

Haematologica

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“…In plants, it also inhibits cyanide-insensitive respiration, peroxidase activity, and protein synthesis (451)(452)(453). Thus, differing sensitivity to the alkaloid among cells devoid of mitochondrial DNA (rho 0 ) and cells with mitochondrial DNA either rho + or rho � has been found in yeasts (440,448,454,455), rho 0 cells being resistant to high concentrations of the drug (450,(456)(457)(458). Thus, differing sensitivity to the alkaloid among cells devoid of mitochondrial DNA (rho 0 ) and cells with mitochondrial DNA either rho + or rho � has been found in yeasts (440,448,454,455), rho 0 cells being resistant to high concentrations of the drug (450,(456)(457)(458).…”

Section: Lycorine Typementioning

confidence: 99%

Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids

Bastida

Lavilla

Viladomat

2006

The Alkaloids: Chemistry and Biology

178

273

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“…Lycorine has been isolated from a variety of plants (see references in Del Giudice et al 1984;Lin et al 1995;Kushida et al 1997;Campbell et al 1998;Davey et al 1998), and shown to possess an inhibitory effect on tumor cell apoptosis (Yui et al 1998), K-ras-transformed fibroblasts (Kushida et al 1997), and multi-drug-resistant phenotype cells (Hua et al 1997). An antimalarial property has also been reported for lycorine (Campbell et al 1998).…”

Section: Discussionmentioning

confidence: 98%

“…In previous papers we have demonstrated that the alkaloid lycorine (Davey et al 1998) is able to differentiate between cells devoid of mitochondrial DNA (rho 0 ) and cells with mitochondrial DNA, either rho + or rho -. Wild-type rho + cells, neutral rho -cells, and moderately suppressive rho -cells are all sensitive to the lycorine; rho 0 cells, however, are resistant to high concentration of the drug (Del Giudice et al 1984).…”

Section: Introductionmentioning

confidence: 99%

Use of lycorine and DAPI staining inSaccharomyces cerevisiaeto differentiate betweenrho⁰andrho^-cells in acce1/Δcce1 nuclear background

Massardo

Zweifel²,

Gunge³

et al. 2000

Can. J. Microbiol.

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In the yeast Saccharomyces cerevisiae, mutants are viable with large deletions (rho-), or even complete loss of the mitochondrial genome (rho0). One class of rho- mutants, which is called hypersuppressive, is characterised by a high transmission of the mutated mitochondrial genome to the diploid progeny when mated to a wild-type (rho+) haploid. The nuclear gene CCE1 encodes a cruciform cutting endonuclease, which is located in the mitochondrion and is responsible for the highly biased transmission of the hypersuppressive rho- genome. CCE1 is a Holliday junction specific endonuclease that resolves recombination intermediates in mitochondrial DNA. The cleavage activity shows a strong preference for cutting after a 5'-CT dinucleotide. In the absence of the CCE1 gene product, the mitochondrial genomes remain interconnected and have difficulty segregating to the daughter cells. As a consequence, there is an increase in the fraction of daughter cells that are rho0. In this paper we demonstrate the usefulness of lycorine, together with staining by 4',6-diamidino-2-phenylindole (DAPI), to assay for the mitotic stability of a variety of mitochondrial genomes. We have found that rho+ and rho- strains that contain CT sequences produce a large fraction of rho0 progeny in the absence of CCE1 activity. Only those rho- mitochondrial genomes lacking the CT recognition sequence are unaffected by the cce1 allele.

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Purification of the Alkaloid Lycorine and Simultaneous Analysis of Ascorbic Acid and Lycorine by Micellar Electrokinetic Capillary Chromatography

Cited by 17 publications

References 40 publications

Lycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate- and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reported CD40-mediated drug resistance

Lycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate- and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reported CD40-mediated drug resistance

Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids

Use of lycorine and DAPI staining inSaccharomyces cerevisiaeto differentiate betweenrho⁰andrho^-cells in acce1/Δcce1 nuclear background

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Purification of the Alkaloid Lycorine and Simultaneous Analysis of Ascorbic Acid and Lycorine by Micellar Electrokinetic Capillary Chromatography

Cited by 17 publications

References 40 publications

Lycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate- and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reported CD40-mediated drug resistance

Lycorine sensitizes CD40 ligand-protected chronic lymphocytic leukemia cells to bezafibrate- and medroxyprogesterone acetate-induced apoptosis but dasatanib does not overcome reported CD40-mediated drug resistance

Chapter 3 Chemical and Biological Aspects of Narcissus Alkaloids

Use of lycorine and DAPI staining inSaccharomyces cerevisiaeto differentiate betweenrho0andrho-cells in acce1/Δcce1 nuclear background

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Use of lycorine and DAPI staining inSaccharomyces cerevisiaeto differentiate betweenrho⁰andrho^-cells in acce1/Δcce1 nuclear background