Biomaterial Database

Comparison of mechanisms responsible for resistance to idarubicin and daunorubicin in multidrug resistant LoVo cell lines. 1994

G Toffoli, and F Simone, and M Gigante, and M Boiocchi

Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano (PN), Italy.

Two human colon carcinoma drug resistant clones (LoVo-IDA-1 and LoVo-IDA-2) were selected by continuous pressure of LoVo parent cell lines to idarubicin (IDA). Both cell sublines exhibited a typical multidrug resistance (MDR) phenotype but, despite IDA selection, the resistance index (RIext) was higher for daunorubicin (DAU) (RIext = 101-112) than for IDA (RIext = 20-23). A similar pattern of cross-resistance was also observed in two (DOX) doxorubicin-selected LoVo cell lines (LoVo-DOX-1 and LoVo-DOX-2). All the MDR cell lines exhibited decreased drug accumulation and increased intracellular drug tolerance as evidenced by the greater intracellular amount of drug required to cause a 50% growth inhibition (IC50int) compared to their parent cell line. The differences between DAU and IDA RIext exhibited by MDR cells were a function of intracellular resistance. DAU IC50int was 13.9 and 14.9 times higher in LoVo-IDA-1,2 and 6.4 and 6.2 in LoVo-DOX-1,2 cell lines, respectively, than in LoVo-sensitive cells, whereas IDA IC50int was only 3.6 and 3.2 times higher in LoVo-IDA-1,2 and 2.2 and 2.3 in LoVo-DOX-1,2 cell lines, respectively. Conversely, variations in IDA accumulation between resistant and sensitive cells were similar to those observed for DAU [the ratios between DAU uptake in sensitive and resistant cells were almost identical (P = NS) to those observed for IDA]. Differences between IDA and DAU intracellular distribution accounted for the relatively higher DAU intracellular resistance. In fact nuclear/cytoplasmic (N/C) DAU fluorescence ratio was higher (P < 0.01) in sensitive (N/C = 3.4 +/- 2.7) than in MDR cells (N/C ranging from 0.31 +/- 0.2 to 0.41 +/- 0.1). In contrast, no significant (P = NS) differences were observed in IDA N/C ratios between sensitive and MDR cells (N/C ranging from 0.16 +/- 0.1 to 0.20 +/- 0.1). In MDR cells, 1-hr VER (10 microM) treatment partially reverted both DAU N/C ratios and intracellular DAU resistance but neither changes in IDA N/C ratios nor variation in intracellular IDA resistance were observed following VER exposure. In conclusion, the greater intracellular drug tolerance that MDR cells show for DAU compared to IDA makes IDA more effective than DAU in MDR cells overexpressing P-glycoprotein (P-gp).

UI	MeSH Term	Description	Entries
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002467	Cell Nucleus	Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)	Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D002999	Clone Cells	A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)	Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D003110	Colonic Neoplasms	Tumors or cancer of the COLON.	Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D003630	Daunorubicin	A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.	Daunomycin,Rubidomycin,Rubomycin,Cerubidine,Dauno-Rubidomycine,Daunoblastin,Daunoblastine,Daunorubicin Hydrochloride,NSC-82151,Dauno Rubidomycine,Hydrochloride, Daunorubicin,NSC 82151,NSC82151
D004095	Dihydropyridines	Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.
D004250	DNA Topoisomerases, Type II	DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.	DNA Topoisomerase (ATP-Hydrolysing),DNA Topoisomerase II,DNA Topoisomerase II alpha,DNA Topoisomerase II beta,DNA Type 2 Topoisomerase,TOP2A Protein,TOP2B Protein,Topoisomerase II,Topoisomerase II alpha,Topoisomerase II beta,Type II DNA Topoisomerase,alpha, Topoisomerase II,beta, Topoisomerase II
D005453	Fluorescence	The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000345	Affinity Labels	Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.	Affinity Labeling Reagents,Labeling Reagents, Affinity,Labels, Affinity,Reagents, Affinity Labeling