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Titolo:
ANTIMICROTUBULE EFFECTS OF THE NOVEL ANTITUMOR BENZOYLPHENYLUREA DERIVATIVE HO-221
Autore:
ANDO N; NAKAJIMA T; MASUDA H; KAWABATA Y; IWAI M; WATANABE M; KAGITANI Y; YAMADA N; TSUKAGOSHI S;
Indirizzi:
GREEN CROSS CO,SAFETY EVALUAT LAB,214-1 YAMASAKI FUKUSAKI CHO HYOGO 67922 JAPAN GREEN CROSS CO,CENT RES LAB HIRAKATA OSAKA 573 JAPAN ISHIHARA SANGYO KAISYA LTD,CENT RES LAB SHIGA 525 JAPAN JAPANESE FDN CANC RES,INST CANC,CTR CANC CHEMOTHERAPY,TOSHIMA KU TOKYO 170 JAPAN
Titolo Testata:
Cancer chemotherapy and pharmacology
fascicolo: 1-2, volume: 37, anno: 1995,
pagine: 63 - 69
SICI:
0344-5704(1995)37:1-2<63:AEOTNA>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
INVITRO; TUBULIN; CELLS; POLYMERIZATION; CARCINOGENS; AGENTS; ASSAY;
Keywords:
HO-221; BENZOYLPHENYLUREA DERIVATIVE; ANTIMICROTUBULE EFFECT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
18
Recensione:
Indirizzi per estratti:
Citazione:
N. Ando et al., "ANTIMICROTUBULE EFFECTS OF THE NOVEL ANTITUMOR BENZOYLPHENYLUREA DERIVATIVE HO-221", Cancer chemotherapy and pharmacology, 37(1-2), 1995, pp. 63-69

Abstract

The antitumor action of HO-221, a novel benzoylphenylurea derivative,was studied. The in vitro cytotoxic strength of HO-221 was investigated, as measured by IC50 values, compared with those of other drugs with different action mechanisms, using Chinese hamster lung (CHL) cells,mouse leukemia L1210 cells and human promyelocytic leukemia HL-60 cells. Morphological alterations following treatment were observed under a phase contrast microscope, and the mitotic index was determined at regular intervals to check for accumulation of metaphase cells. HO-221 was found to have a very strong toxic effect on all cell types, equal to that of the spindle poisons used as controls. HO-221 also produced the same specific morphological changes as the spindle poisons, with asignificant accumulation of metaphase cells. A chromosome analysis oftreated cells showed that HO-221 frequently induced polyploid and aneuploid cells, but without accompanying chromosome-breaking activity. An in vivo mouse bone marrow micronucleus assay was also carried out. The assay allowed the in vivo identification of a chromosome breaker ora spindle poison through the measurement of the relative sizes of micronuclei produced and erythrocytes. HO-221 was found frequently to induce relatively large micronuclei, an action regarded as specific to spindle poisons. It was thus demonstrated that HO-221 acts as a spindle poison both in vitro and in vivo. In order to investigate the mechanism of this action, a study of tubulin assembly using purified calf brain tubulin was carried out, which demonstrated clearly that HO-221 inhibits microtubule assembly. A detailed investigation of the action mechanism of HO-221 as a spindle poison is now called for.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/21 alle ore 02:14:39