BIOMAT Database Logo BIOMAT Database Logo

Effects of 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin and doxorubicin on the survival, DNA integrity, and nucleolar morphology of human leukemia cells in vitro. 1986

K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman

The potential mechanisms of the extremely potent anthracycline analogue 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin (MRA-CN) have been compared with those of doxorubicin (DOX) by examination of drug effects on colony formation, macromolecular synthesis, DNA integrity, and ultrastructure of human leukemia cells in vitro. Following a 1-h exposure, MRA-CN was found to be 1400-fold more cytocidal than DOX which correlated with the drugs' inhibitory effects on DNA and total RNA synthesis. Treatment with MRA-CN resulted in a dose-dependent production of DNA interstrand cross-links as quantified by alkaline elution. One-h treatments with DOX or 3'-deamino-3'-(4-morpholinyl) doxorubicin (the non-cyano-containing analogue of MRA-CN) produced no DNA-DNA cross-links; rather they produced protein-concealed DNA single-strand breaks. After removal of MRA-CN, the DNA of KBM-3 cells displayed time-dependent fragmentation as indicated by rapid DNA filter elution during the pH 10 lysis step which preceded pH 12 elution. Within 4 h of MRA-CN exposure (10 nM, 1 h), 50% of the cellular DNA was in the lysis fraction. By 24 h, all the cellular DNA was in this fraction. MRA-CN (10 nM), 3'-deamino-3'-(4-morpholinyl)doxorubicin (1 microM), and actinomycin D (1 microM), but not DOX (3 mircroM), each produced distinctive nucleolar macrosegregation, indicating an effect on rRNA synthesis. The alpha-CN substituent on the morpholinyl moiety of MRA-CN appears to be responsible for the unique antitumor potency of this anthracycline. Nucleolar macrosegregation is probably associated with the morpholinyl moiety and is independent of the alpha-CN substituent.

UI MeSH Term Description Entries
D007938 Leukemia A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006) Leucocythaemia,Leucocythemia,Leucocythaemias,Leucocythemias,Leukemias
D002466 Cell Nucleolus Within most types of eukaryotic CELL NUCLEUS, a distinct region, not delimited by a membrane, in which some species of rRNA (RNA, RIBOSOMAL) are synthesized and assembled into ribonucleoprotein subunits of ribosomes. In the nucleolus rRNA is transcribed from a nucleolar organizer, i.e., a group of tandemly repeated chromosomal genes which encode rRNA and which are transcribed by RNA polymerase I. (Singleton & Sainsbury, Dictionary of Microbiology & Molecular Biology, 2d ed) Plasmosome,Cell Nucleoli,Nucleoli, Cell,Nucleolus, Cell,Plasmosomes
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
D003609 Dactinomycin A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015) Actinomycin,Actinomycin D,Meractinomycin,Cosmegen,Cosmegen Lyovac,Lyovac-Cosmegen,Lyovac Cosmegen,Lyovac, Cosmegen,LyovacCosmegen
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000903 Antibiotics, Antineoplastic Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. Antineoplastic Antibiotics,Cytotoxic Antibiotics,Antibiotics, Cytotoxic
D012334 RNA, Neoplasm RNA present in neoplastic tissue. Neoplasm RNA

Related Publications

K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
Doxorubicin and the alkylating anthracycline 3'-deamino-3'-(3-cyano-4-morpholinyl) doxorubicin: comparative in vitro potency against leukemia and bone marrow cells.
May 1988, Journal of the National Cancer Institute,
K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
N-(2-hydroxyethyl)doxorubicin from hydrolysis of 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin.
October 1986, Journal of medicinal chemistry,
K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
Toxicity of 3'-deamino-3'-(3-cyano-4-morpholinyl) doxorubicin and doxorubicin in nude mice bearing human tumour xenografts.
January 1991, Anticancer research,
K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
DNA crosslinking by 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin in HT-29 human colon carcinoma cells in vitro.
August 1985, Biochemical and biophysical research communications,
K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
Effects of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin and structural analogues on DNA in HT-29 human colon carcinoma cells.
November 1987, Cancer research,
K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
Dissociation between in vitro cytotoxicity and in vivo cardiotoxicity of two new anthracyclines: 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin and 4'-deoxy-4'-iodo-doxorubicin.
January 1994, Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer,
K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
Uptake and binding of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin and 3'-(4-morpholinyl)-3'-deaminoadriamycin in L5178Y lymphoblasts in vitro.
January 1990, Cancer communications,
K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
Phase I clinical and pharmacokinetic study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762).
May 1995, Cancer research,
K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
Characterization of the DNA-DNA cross-linking activity of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin.
December 1989, Cancer research,
K Wassermann, and L A Zwelling, and T D Mullins, and L E Silberman, and B S Andersson, and M Bakic, and E M Acton, and R A Newman
Cellular pharmacology of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin and structural analogues in human colon carcinoma HT-29 cells in vitro.
August 1987, Cancer research,
Copied contents to your clipboard!