Inactivation by the mitotic inhibitor NY 3170 of human cells in vitro

Wibe, Einar; Oftebro, R.

doi:10.1038/bjc.1979.169

Cited by 11 publications

(6 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This property is somewhat different from that earlier reported for NY 3170 (5). In that case about 50~ of the cells were able to form colonies even after 4 hr mitotic arrest in the presence of a concentration (0.2 mM) giving nearly complete metaphase arrest.…”

Section: Discussioncontrasting

confidence: 90%

“…One of these, 1-propargyl-5-chloropyrimidin-2-one (NY 3170), * Fellow of the Norwegian Cancer Society (Landsforeningen mot Kreft). has been studied closely in vitro both on cells grown in monolayer (4)(5)(6) and in spheroids (7). This compound was shown to induce a metaphase arresting effect in the concentration range 0.05 to 0.4 mM on cells grown in monolayer.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mitotic arrest and interphase inhibition induced by the pyrimidine sulfoxide NY 4138

Pettersen¹,

Nome²,

Dornish³

et al. 1985

Invest New Drugs

View full text Add to dashboard Cite

Phase-specific cell-cycle inhibitory effects of the sulfoxide 5-bromo-2-(2-thienylmethyl)sulfinyl-pyrimidine (NY 4138) was studied on synchronized human NHIK 3025 cells cultivated in vitro. When added to exponentially growing cells, NY 4138 induced an accumulation of metaphases. The metaphase arrest was, however, not efficient immediately after addition of the compound. While a few telophases were still present 3 h after addition of 0.1 mM, no telophases were seen 6 h after addition. Most cells exposed to metaphase arrest by NY 4138 lost their ability to form colonies. We therefore characterize the metaphase arrest induced by this drug as irreversible. For concentrations above 0.5 mM phase specific cell cycle inhibition was also observed during interphase. Cells treated in G1 only were not delayed in G1 but were delayed in S and in G2. Cells treated in S only were also delayed in S, but to a smaller extent than the cells treated in G1 only. Cells treated with 0.1 mM NY 4138 for a period of 4 h in either G1 or in S showed no significant prolongation of the subsequent mitosis (i.e. the drug was in this case not present during mitosis). However, about 20% of the cells in this case divided to form 3 daughter cells of which 1 had a normal G1 DNA-content, 1 had 1/3 and 1 had 2/3 of a normal G1 DNA-content.

show abstract

Section: Discussioncontrasting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Mitotic arrest and interphase inhibition induced by the pyrimidine sulfoxide NY 4138

Pettersen¹,

Nome²,

Dornish³

et al. 1985

Invest New Drugs

View full text Add to dashboard Cite

show abstract

“…Results with the metahalone NY 3170 are quite different. Reports have shown that mitotic arrest caused by NY 3170 is induced if, and only if, this drug is present during mitosis (5,6). During continuous treatment with NY 4137 (Fig.…”

Section: Discussionmentioning

confidence: 93%

Effects of the new mitotic inhibitor pyrimidinsulfone NY 4137 on human cells in vitro and on colchicine binding to tubulin

et al. 1986

View full text Add to dashboard Cite

The effect of 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137) on cells of the human line NHIK 3025 was investigated. It was shown that NY 4137 induces cell cycle specific inhibition in metaphase. A dose-dependent prolongation of metaphase was found and the fraction of cells able to escape metaphase arrest declined gradually as the concentration of NY 4137 increased. A total block in metaphase was achieved with 0.016 mM and higher concentrations of NY 4137. Interphase was also prolonged in cells treated with 0.016 mM. Inhibition of valine incorporation by NY 4137 was also found to be dose-dependent. Following a 2-h exposure to 0.2 mM NY 4137 valine incorporation was inhibited by 80-85%. Inhibition of colchicine and vincristine binding to purified tubulin was also investigated. Double reciprocal plot and gel filtration chromatography showed that NY 4137 competitively inhibited colchicine binding to DEAE-cellulose purified tubulin. NY 4137 had no effect on vincristine binding to tubulin. The binding of NY 4137 to tubulin at or near the colchicine binding site may be responsible for the metaphase arrest.

show abstract

“…I-Propargyl-5-chloropyrimidin-2-one (NY 3170) is a mitotic inhibitor which causes reversible metaphase inhibition in cultured cells (Wibe & Oftebro, 1979). A sufficient, but necessary prerequisite for metaphase inhibition is that the drug be present during mitosis (Wibe et al, 1979).…”

mentioning

confidence: 99%

“…A sufficient, but necessary prerequisite for metaphase inhibition is that the drug be present during mitosis (Wibe et al, 1979). The parent compound 5-chloropyrimidin-2-one (NY 3000) also induces metaphase arrest in cultured cells (Wibe et al, 1978).…”

mentioning

confidence: 99%

Synergistic cell inactivation by cis-dichlorodiammineplatinum in combination with 1-propargyl-5-chloropyrimidin-2-one

Dornish

Pettersen²,

Oftebro³

1987

Br J Cancer

Self Cite

View full text Add to dashboard Cite

Summary A synergistic effect with respect to inactivation of human NHIK 3025 cells cultured in vitro was displayed when treatment with cis-dichlorodiammineplatinum(II) (cis-DDP) and the mitotic inhibitor 1-propargyl-5-chloropyrimidin-2-one (NY 3170) were given in simultaneous combination. Cell inactivation was measured by loss of colony-forming ability. Treatment with NY 3170 alone produced no significant inactivation at concentrations up to 2mM. However, treatment with NY 3170 in combination with cis-DDP induced increased cell inactivating effects equal to a doubling of either the concentration of cis-DDP or treatment time. Scheduling of NY 3170 treatment in relationship to a 1 h cis-DDP pulse revealed that synergism occurred only when the two drugs were present simultaneously. The inactivating effect of lOpM cis-DDP in combination with 2mM NY 3170 given to synchronized NHIK 3025 cells at various stages of the cell cycle was also determined. For cells treated in S or in G2 + M cell survival was reduced by a factor of 5 after a I h treatment with the drug combination as compared to similar treatment with cis-DDP alone. The cells appeared to be most sensitive at the time of initiation of DNA synthesis. Here cell survival was reduced by a factor of 100 following treatment with the drug combination than following treatment with cis-DDP alone. Measurement of cell-associated platinum by atomic absorption spectroscopy indicated that cellular uptake of cis-DDP was increased when NY 3170 was simultaneously present during drug treatment.

show abstract

Inactivation by the mitotic inhibitor NY 3170 of human cells in vitro

Cited by 11 publications

References 7 publications

Mitotic arrest and interphase inhibition induced by the pyrimidine sulfoxide NY 4138

Mitotic arrest and interphase inhibition induced by the pyrimidine sulfoxide NY 4138

Effects of the new mitotic inhibitor pyrimidinsulfone NY 4137 on human cells in vitro and on colchicine binding to tubulin

Synergistic cell inactivation by cis-dichlorodiammineplatinum in combination with 1-propargyl-5-chloropyrimidin-2-one

Contact Info

Product

Resources

About