Biomaterial Database

2,3-dehydrosilybin is a better DNA topoisomerase I inhibitor than its parental silybin. 2009

Piyanut Thongphasuk, and Wolfgang Stremmel, and Walee Chamulitrat

Department of Gastroenterology and Infectious Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 345 EG, Heidelberg, Germany.

BACKGROUND We have shown that compared with silybin, 2,3-dehydrosilybin (DHS) exhibits more potent in vitro anticancer activities alone or in combination with tumor necrosis factor (TNF)-alpha. Since TNF-alpha sensitization is related to DNA topoisomerase (topo) inhibition, DHS may be a potent topo inhibitor. METHODS Under significant apoptosis induction by DHS, we measured specific topo I activity in nuclear extracts or purified enzyme. RESULTS Treatment of more transformed FIB cells with 30 microM DHS for 24 h caused significant decreases in topo I activity in nuclear extracts while silybin did not have any effects. Less transformed EPI cells were more resistant against DHS-induced topo I inhibition. Inhibitory effects of topo I activity by DHS were also found in cell-free assays using purified topo I, whereas silybin again did not have any effects. CONCLUSIONS DHS is a potent topo I inhibitor rendering its ability to sensitize TNF-alpha for enhanced cytotoxicity.

UI	MeSH Term	Description	Entries
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003627	Data Interpretation, Statistical	Application of statistical procedures to analyze specific observed or assumed facts from a particular study.	Data Analysis, Statistical,Data Interpretations, Statistical,Interpretation, Statistical Data,Statistical Data Analysis,Statistical Data Interpretation,Analyses, Statistical Data,Analysis, Statistical Data,Data Analyses, Statistical,Interpretations, Statistical Data,Statistical Data Analyses,Statistical Data Interpretations
D004264	DNA Topoisomerases, Type I	DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.	DNA Nicking-Closing Protein,DNA Relaxing Enzyme,DNA Relaxing Protein,DNA Topoisomerase,DNA Topoisomerase I,DNA Topoisomerase III,DNA Topoisomerase III alpha,DNA Topoisomerase III beta,DNA Untwisting Enzyme,DNA Untwisting Protein,TOP3 Topoisomerase,TOP3alpha,TOPO IIIalpha,Topo III,Topoisomerase III,Topoisomerase III beta,Topoisomerase IIIalpha,Topoisomerase IIIbeta,DNA Nicking-Closing Proteins,DNA Relaxing Enzymes,DNA Type 1 Topoisomerase,DNA Untwisting Enzymes,DNA Untwisting Proteins,Topoisomerase I,Type I DNA Topoisomerase,III beta, Topoisomerase,III, DNA Topoisomerase,III, Topo,III, Topoisomerase,IIIalpha, TOPO,IIIalpha, Topoisomerase,IIIbeta, Topoisomerase,Topoisomerase III, DNA,Topoisomerase, TOP3,beta, Topoisomerase III
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077385	Silybin	The major active component of silymarin flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum; it is used in the treatment of HEPATITIS; LIVER CIRRHOSIS; and CHEMICAL AND DRUG INDUCED LIVER INJURY, and has antineoplastic activity; silybins A and B are diastereomers.	2,3-Dehydrosilybin,Alepa-forte,Ardeyhepan,Cefasilymarin,Durasilymarin,Hepa-Merz Sil,Hepa-loges,HepaBesch,Hepar-Pasc,Heparsyx,Heplant,Lagosa,Legalon Forte,Silibin,Silibinin,Silibinin A,Silibinin B,Silybin A,Silybin B,Silybinin,2,3 Dehydrosilybin,Alepa forte,Hepa Merz Sil,Hepa loges,Hepar Pasc
D000970	Antineoplastic Agents	Substances that inhibit or prevent the proliferation of NEOPLASMS.	Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D012838	Silymarin	A mixture of flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum. It consists primarily of silybin and its isomers, silicristin and silidianin. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent.	Carsil,Karsil,Legalon,Silimarin
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D014409	Tumor Necrosis Factor-alpha	Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.	Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D045744	Cell Line, Tumor	A cell line derived from cultured tumor cells.	Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines