Biomaterial Database

Effects of 9-OH-ellipticine on cell survival, macromolecular syntheses, and cell cycle progression in sensitive and resistant Chinese hamster lung cells. 1985

J Y Charcosset, and J P Bendirdjian, and M F Lantieri, and A Jacquemin-Sablon

In an effort to understand the mechanism of action of the DNA-intercalating antitumor agent 9-hydroxyellipticine (9-OH-E), we have examined the effects of this drug on the cell survival, macromolecular syntheses, and cell cycle progression in sensitive and resistant cells. Our results show that 9-OH-E toxicity on sensitive and resistant cells involves different mechanisms of action: the drug toxicity in the sensitive cells appears to result from lethal lesions mediated through the interaction of the drug with an intracellular protein, independently of any effect of the drug on the macromolecular syntheses; in the resistant cells, the cell death occurs concomitantly with the inhibition of these syntheses. Cell cycle progression analysis after 9-OH-E treatment showed that, in the sensitive cells, the drug is inducing a G1 and a G2 block, which are both released in the presence of 1 mM caffeine, without any effect on the 9-OH-E toxicity. In the resistant cells, a G2 block was also observed but only when the cells were resuming their growth after about a 30- to 40-h growth arrest. Caffeine release of this block, which again had no effect on 9-OH-E toxicity, was only observed when it was added from 40 to 60 h after 9-OH-E treatment, when the cells resumed their growth. Finally in the sensitive cells, cycloheximide exerted an inhibitory effect on 9-OH-E toxicity when it was added before and during the cell exposure to the drug. This effect was interpreted as indicating that 9-OH-E toxicity in the sensitive cells relies on a protein which is not induced by the drug but has to be present in the cells when the drug is added. The possible implication of DNA topoisomerases in 9-OH-E toxicity mechanism is discussed.

UI	MeSH Term	Description	Entries
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D009696	Nucleic Acids	High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages.	Nucleic Acid,Acid, Nucleic,Acids, Nucleic
D002110	Caffeine	A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.	1,3,7-Trimethylxanthine,Caffedrine,Coffeinum N,Coffeinum Purrum,Dexitac,Durvitan,No Doz,Percoffedrinol N,Percutaféine,Quick-Pep,Vivarin,Quick Pep,QuickPep
D002453	Cell Cycle	The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.	Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
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
D003412	Cricetulus	A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.	Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D003513	Cycloheximide	Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.	Actidione,Cicloheximide
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
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