Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Determinants Of Etoposide Cytotoxicity In Vitro

R. Lock
Published 1994 · Chemistry

Save to my Library
Download PDF
Analyze on Scholarcy
The epipodophyllotoxin etoposide, which has a broad range of antitumor activity (1,2), is used in combination chemotherapy regimens for the treatment of a variety of solid tumors, lymphomas and leukemias (3). Based almost exclusively on in vitro data, the mechanism of etoposide cytotoxicity has been defined to involve primarily the induction of protein-associated DNA strand breaks (cleavable complexes) via interaction with the nuclear enzyme, DNA topoisomerase II (topo II). These data are summarized as follows: Intracellular topo II levels and activity, or the expression of drug resistant forms of topo II, show a good correlation with the quantity of etoposide-induced DNA strand breaks and cytotoxicity in a variety of mammalian cell lines (4–8); etoposide inhibits the activity of topo II in vitro (9) and causes extensive DNA fragmentation in the presence of purified calf thymus topo II (10,11) with the enzyme attached to the 5′ phosphoryl end of the broken DNA strand (10); overexpression of plasmid-borne topo II in yeast leads to etoposide hypersensitivity (12).
This paper references
Estrogen-induced potentiation of DNA damage and cytotoxicity in human breast cancer cells treated with topoisomerase II-interactive antitumor drugs.
R. Epstein (1988)
Single- and double-strand DNA breakage and repair in human lung adenocarcinoma cells exposed to etoposide and teniposide.
B. Long (1985)
Possible role for p34cdc2 kinase in etoposide-induced cell death of Chinese hamster ovary cells.
R. Lock (1990)
Induction of apoptosis in fibroblasts by c-myc protein
G. Evan (1992)
bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship
A. Strasser (1991)
Abrogation of etoposide-mediated cytotoxicity by cycloheximide.
K. C. Chow (1988)
Etoposide (VP-16-213). Current status of an active anticancer drug.
P. O'dwyer (1985)
Cytofluorometric studies on the action of podophyllotoxin and epipodophyllotoxins (VM-26, VP-16-213) on the cell cycle traverse of human lymphoblasts
A. Krishan (1975)
Differential requirement of DNA replication for the cytotoxicity of DNA topoisomerase I and II inhibitors in Chinese hamster DC3F cells.
C. Holm (1989)
bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes
C. Sentman (1991)
Kinetics of micronucleus formation in relation to chromosomal aberrations in mouse bone marrow.
M. Hayashi (1984)
Effect of an epipodophyllotoxin derivative (VP 16-213) on macromolecular synthesis and mitosis in mastocytoma cells in vitro.
A. Grieder (1974)
Etoposide (VP-16) : current status and new developments
B. Issell (1984)
Molecular and Clinical Advances in Anticancer Drug Resistance
R. Ozols (1991)
Inhibition of p34cdc2 kinase activity by etoposide or irradiation as a mechanism of G2 arrest in Chinese hamster ovary cells.
R. Lock (1990)
The effect of adriamycin on the cell cycle traverse of a human lymphoid cell line.
B. Barlogie (1976)
Cell death induced by topoisomerase inhibitors. Role of calcium in mammalian cells.
R. Bertrand (1991)
Inhibition by 4'-demethyl-epipodophyllotoxin 9-(4,6-O-2-thenylidene-beta-D-glucopyranoside) of human lymphoblast cultures in G2 phase of the cell cycle.
N. C. Misra (1975)
Monitoring of sister chromatid exchange and micronuclei as biological endpoints.
M. Sorsa (1984)
Potentiation of topoisomerase inhibitor-induced DNA strand breakage and cytotoxicity by tumor necrosis factor: enhancement of topoisomerase activity as a mechanism of potentiation.
T. Utsugi (1990)
Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice
R. Kim (1992)
Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons.
P. D'Arpa (1990)
The one-cell mouse embryo: cell cycle-dependent radiosensitivity and development of chromosomal anomalies in postradiation cell cycles.
U. Weissenborn (1988)
Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage.
W. Ross (1984)
Relationship of c‐myc gene copy number and gene expression: Cellular effects of elevated c‐myc protein
M. Pallavicini (1990)
Attenuated topoisomerase II content directly correlates with a low level of drug resistance in a Chinese hamster ovary cell line.
C. Webb (1991)
Amsacrine and etoposide hypersensitivity of yeast cells overexpressing DNA topoisomerase II.
J. Nitiss (1992)
Mechanism of epipodophyllotoxin-induced cell death in poly(adenosine diphosphate-ribose) synthesis-deficient V79 Chinese hamster cell lines.
S. Chatterjee (1990)
Depletion of topoisomerase II in isolated nuclei during a glucose-regulated stress response.
J. Shen (1989)
Proliferation-dependent topoisomerase II content as a determinant of antineoplastic drug action in human, mouse, and Chinese hamster ovary cells.
D. Sullivan (1987)
Assessment of cytogenetic damage by quantitation of micronuclei in human peripheral blood erythrocytes.
R. Schlegel (1986)
Inhibition of p34cdc2 kinase activation, p34cdc2 tyrosine dephosphorylation, and mitotic progression in Chinese hamster ovary cells exposed to etoposide.
R. Lock (1992)
Radiation-induced division delay in Chinese hamster ovary fibroblast and carcinoma cells: dose effect and ploidy.
B. Kimler (1981)
Effects of asbestos fibers on cell division, cell survival, and formation of thioguanine-resistant mutants in Chinese hamster ovary cells.
K. Kenne (1986)
Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note.
S. Kaufmann (1989)
Caffeine-induced modulation of the lethal action of X rays on Chinese hamster V79 cells.
J. Labanowska (1988)
The action of caffeine on X-irradiated HeLa cells. III. Enhancement of X-ray-induced killing during G2 arrest.
P. Busse (1978)
Differential induction of secondary DNA fragmentation by topoisomerase II inhibitors in human tumor cell lines with amplified c-myc expression.
R. Bertrand (1991)
Inhibition of the DNA catenation activity of type II topoisomerase by VP16-213 and VM26.
A. Minocha (1984)
Overproduction of topoisomerase II in an ataxia telangiectasia fibroblast cell line: comparison with a topoisomerase II-overproducing hamster cell mutant.
S. Davies (1989)
The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae.
T. Weinert (1988)
Resistance to inhibitors of DNA topoisomerases.
D. Sullivan (1991)
Involvement of intracellular ATP in cytotoxicity of topoisomerase II-targetting antitumor drugs.
G. Kupfer (1987)
Mechanism by which caffeine potentiates lethality of nitrogen mustard.
C. Lau (1982)
Cancer : Principles and Practice of Oncology
V. Devita (1982)
Amsacrine-induced lesions in DNA and their modulation by novobiocin and 2,4-dinitrophenol.
M. Shibuya (1991)
Cloning and characterization of the 5'-flanking region of the human topoisomerase II alpha gene.
D. Hochhauser (1992)
G2 block induced by DNA crosslinking agents and its possible consequences.
J. Konopa (1988)
Different drugs arrest cells at a number of distinct stages in G2
Robert A. Tobey (1975)
Relationship between topoisomerase II level and chemosensitivity in human tumor cell lines.
A. Fry (1991)
Survival and cycle-progression delay of human lymphoma cells in vitro exposed to VP-16-213.
B. Drewinko (1976)
Cytotoxic synergism between trimetrexate and etoposide. Evidence that trimetrexate potentiates etoposide-induced protein-associated DNA strand breaks in L1210 leukemia cells through alterations in intracellular ATP concentrations.
D. Fry (1990)
Nonintercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II.
G. L. Chen (1984)

Semantic Scholar Logo Some data provided by SemanticScholar