2,3-Dehydrosilybin Is a Better DNA Topoisomerase I Inhibitor than Its Parental Silybin

Thongphasuk, Piyanut; Stremmel, Wolfgang; Chamulitrat, Waleé

doi:10.1159/000175466

Cited by 19 publications

(12 citation statements)

References 43 publications

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“…For instance, 2,3-dehydrosilydianin was shown to inhibit tert -butyl hydroperoxide-induced lipid peroxidation with a higher potency than silydianin [11]. Similarly, 2,3-dehydrosilybin is a more potent inhibitor of DNA topoisomerase I [30], cytochrome P450 1A1 [31] and the glucose transporter GLUT4 [32] than silybin.…”

Section: Discussionmentioning

confidence: 99%

Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells

et al. 2017

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Silybum marianum (milk thistle) is a medicinal plant used for the treatment of various liver disorders. This study examined whether the main flavonolignans from S. marianum (i.e. silybin, silychristin, silydianin) and their 2,3-dehydro derivatives (i.e. 2,3-dehydrosilybin, 2,3-dehydrosilychristin, 2,3-dehydrosilydianin) activate the Nrf2 pathway, which regulates the expression of genes encoding many cytoprotective enzymes, including NAD(P)H:quinone oxidoreductase 1 (NQO1). After 48 h of exposure, 2,3-dehydrosilydianin at concentrations of 25 μM and higher significantly elevated the activity of NQO1 in murine hepatoma Hepa1c1c7 cells. In contrast, other tested compounds at non-cytotoxic concentrations had a mild or negligible effect on the NQO1 activity. Using a luciferase reporter assay, 2,3-dehydrosilydianin was found to significantly activate transcription via the antioxidant response element in stably transfected human AREc32 reporter cells. Moreover, 2,3-dehydrosilydianin caused the accumulation of Nrf2 and significantly induced the expression of the Nqo1 gene at both the mRNA and protein levels in Hepa1c1c7 cells. We found that 2,3-dehydrosilydianin also increased to some extent the expression of other Nrf2 target genes, namely of the heme oxygenase-1 gene (Hmox1) and the glutamate-cysteine ligase modifier subunit gene (Gclm). We conclude that 2,3-dehydrosilydianin activates Nrf2 and induces Nrf2-mediated gene expression in Hepa1c1c7 cells.

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Section: Discussionmentioning

confidence: 99%

Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells

et al. 2017

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“…It is a classic topoisomerase II poison because these adducts inhibit the function of this enzyme which catalyzes the unwinding of DNA for transcription and replication. The intercalation of CAT into DNA may well obstruct the normal interaction and identification between DNA sequences and functional protein factors [31,32,33,34]. Tylocrebrine, another phenanthroindolizidine compound, was previously reported to inhibit RNA synthesis as measured by the amount of 14 C-labeled uridine incorporation [8].…”

Section: Discussionmentioning

confidence: 99%

Interaction Studies of an Anticancer Alkaloid, (+)-(13aS)-Deoxytylophorinine, with Calf Thymus DNA and Four Repeated Double-Helical DNAs

Liu¹,

Li³

et al. 2011

Chemotherapy

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Background: Phenanthroindolizidine alkaloids are a family of plant-derived compounds with significant antineoplastic activity. The specific biomolecular targets of these alkaloids have not yet been clearly identified. (+)-(13aS)-deoxytylophorinine is a new phenanthroindolizidine alkaloid originally extracted from the roots of Tylophora atrofolliculata and Tylophora ovata in our institute. (+)-(13aS)-deoxytylophorinine exerts both in vitro and in vivoanticancer activities. Methods: The in vivo anticancer effects and toxicity of this compound were investigated in mice, and interactions between this compound and double-helical DNA sequences were studied in detail with circular dichroic spectroscopy and fluorescence spectroscopy. Viscosity measurements were applied to check the interactive mode between this compound and DNA. Results: Potent anticancer effects were observed in vivo. Also, concentration-dependent interactions were observed and this compound seemed to interact in a sequence-specific manner with AT-repeated sequences of double-helical DNA. Such interactions were proved to be intercalating by viscosity measurements. Conclusions: Anticancer alkaloid (+)-(13aS)-deoxytylophorinine can have sequence-specific interactions with DNA in an intercalating manner.

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“…Silybin occurs in silymarin as an approximately equimolar mixture of two diastereoisomers: silybin A ( 1a ) and silybin B ( 1b ) (Figure 1) [2]. 2,3-Dehydrosilybin ( 6 ) occurs in silymarin in minor amounts (also as a mixture of enantiomers) presumably resulting from spontaneous oxidation of silybin [3], and it has significantly higher anticancer [4,5] and antioxidant [6,7] activity than silybin.…”

Section: Introductionmentioning

confidence: 99%

Chemo-Enzymatic Synthesis of Silybin and 2,3-Dehydrosilybin Dimers

et al. 2014

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Divalent or multivalent molecules often show enhanced biological activity relative to the simple monomeric units. Here we present enzymatically and chemically prepared dimers of the flavonolignans silybin and 2,3-dehydrosilybin. Their electrochemical behavior was studied by in situ and ex situ square wave voltammetry. The oxidation of monomers and dimers was similar, but adsorption onto the electrode and cell surfaces was different. A 1,1-diphenyl-2-picrylhydrazyl (DPPH) and an inhibition of microsomal lipoperoxidation assay were performed with same trend of results for silybin and 2,3-dehydrosilybin dimers. Silybin dimer showed better activity than the monomer, while on the contrary 2,3-dehydrosilybin dimer presented weaker antioxidant/antilipoperoxidant activity than its monomer. Cytotoxicity was evaluated on human umbilical vein endothelial cells, normal human adult keratinocytes, mouse fibroblasts (BALB/c 3T3) and human liver hepatocellular carcinoma cell line (HepG2). Silybin dimer was more cytotoxic than the parent compound and in the case of 2,3-dehydrosilybin its dimer showed weaker cytotoxicity than the monomer.

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2,3-Dehydrosilybin Is a Better DNA Topoisomerase I Inhibitor than Its Parental Silybin

Cited by 19 publications

References 43 publications

Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells

Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells

Interaction Studies of an Anticancer Alkaloid, (+)-(13aS)-Deoxytylophorinine, with Calf Thymus DNA and Four Repeated Double-Helical DNAs

Chemo-Enzymatic Synthesis of Silybin and 2,3-Dehydrosilybin Dimers

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