3′-Deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin conquers multidrug resistance by rapid influx following higher frequency of formation of DNA single-and double-strand breaks

Naoya Horichi, Haim Tapiero, Yoshikazu Sugimoto, Masami Bungo, Masahiko Nishiyama, Alain Fourcade, Theodore J. Lampidis, Kazuo Kasahara, Yasutsuna Sasaki, Terumi Takahashi, Nagahiro Saijo

研究成果: Article

36 引用 (Scopus)

抄録

The mechanism of action of 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) was examined in a human leukemia cell line (K562) and its Adriamycin (ADM)-resistant subline (K562/ADM). ADM and MX2 showed an equivalent antitumor effect against K562. K562/ADM was highly resistant to ADM. In cellular pharmacokinetic studies, MX2 showed faster and greater influx than did ADM in both K562 and K562/ADM. The efflux of ADM was rapid in K562/ADM but not in K562. On the other hand, the efflux of MX2 was rapid in both cell lines. The formation of DNA single-strand breaks and double-strand breaks by ADM was significantly lower in K562/ADM than K562. On the other hand, formation of those breaks by MX2 was not decreased. Although some of the DNA breaks induced by MX2 were resealed, there was no difference in the degree of resealing in K562 and K562/ADM cells. On the other hand, most of the small number of DNA breaks in K562/ADM induced by ADM were resealed. The topoisomerase II activity in K562 and K562/ADM was not significantly different. It is concluded that MX2 conquers multidrug resistance by rapid influx following a higher frequency of formation of DNA single- and double-strand breaks in K562/ADM cells.

元の言語English
ページ(範囲)4698-4701
ページ数4
ジャーナルCancer Research
50
発行部数15
出版物ステータスPublished - 1990 8 1
外部発表Yes

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Single-Stranded DNA Breaks
Morpholinos
Double-Stranded DNA Breaks
Multiple Drug Resistance
Doxorubicin
DNA Breaks
K562 Cells
Cell Line
Type II DNA Topoisomerase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

これを引用

3′-Deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin conquers multidrug resistance by rapid influx following higher frequency of formation of DNA single-and double-strand breaks. / Horichi, Naoya; Tapiero, Haim; Sugimoto, Yoshikazu; Bungo, Masami; Nishiyama, Masahiko; Fourcade, Alain; Lampidis, Theodore J.; Kasahara, Kazuo; Sasaki, Yasutsuna; Takahashi, Terumi; Saijo, Nagahiro.

:: Cancer Research, 巻 50, 番号 15, 01.08.1990, p. 4698-4701.

研究成果: Article

Horichi, N, Tapiero, H, Sugimoto, Y, Bungo, M, Nishiyama, M, Fourcade, A, Lampidis, TJ, Kasahara, K, Sasaki, Y, Takahashi, T & Saijo, N 1990, '3′-Deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin conquers multidrug resistance by rapid influx following higher frequency of formation of DNA single-and double-strand breaks', Cancer Research, 巻. 50, 番号 15, pp. 4698-4701.
Horichi, Naoya ; Tapiero, Haim ; Sugimoto, Yoshikazu ; Bungo, Masami ; Nishiyama, Masahiko ; Fourcade, Alain ; Lampidis, Theodore J. ; Kasahara, Kazuo ; Sasaki, Yasutsuna ; Takahashi, Terumi ; Saijo, Nagahiro. / 3′-Deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin conquers multidrug resistance by rapid influx following higher frequency of formation of DNA single-and double-strand breaks. :: Cancer Research. 1990 ; 巻 50, 番号 15. pp. 4698-4701.
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abstract = "The mechanism of action of 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) was examined in a human leukemia cell line (K562) and its Adriamycin (ADM)-resistant subline (K562/ADM). ADM and MX2 showed an equivalent antitumor effect against K562. K562/ADM was highly resistant to ADM. In cellular pharmacokinetic studies, MX2 showed faster and greater influx than did ADM in both K562 and K562/ADM. The efflux of ADM was rapid in K562/ADM but not in K562. On the other hand, the efflux of MX2 was rapid in both cell lines. The formation of DNA single-strand breaks and double-strand breaks by ADM was significantly lower in K562/ADM than K562. On the other hand, formation of those breaks by MX2 was not decreased. Although some of the DNA breaks induced by MX2 were resealed, there was no difference in the degree of resealing in K562 and K562/ADM cells. On the other hand, most of the small number of DNA breaks in K562/ADM induced by ADM were resealed. The topoisomerase II activity in K562 and K562/ADM was not significantly different. It is concluded that MX2 conquers multidrug resistance by rapid influx following a higher frequency of formation of DNA single- and double-strand breaks in K562/ADM cells.",
author = "Naoya Horichi and Haim Tapiero and Yoshikazu Sugimoto and Masami Bungo and Masahiko Nishiyama and Alain Fourcade and Lampidis, {Theodore J.} and Kazuo Kasahara and Yasutsuna Sasaki and Terumi Takahashi and Nagahiro Saijo",
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T1 - 3′-Deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin conquers multidrug resistance by rapid influx following higher frequency of formation of DNA single-and double-strand breaks

AU - Horichi, Naoya

AU - Tapiero, Haim

AU - Sugimoto, Yoshikazu

AU - Bungo, Masami

AU - Nishiyama, Masahiko

AU - Fourcade, Alain

AU - Lampidis, Theodore J.

AU - Kasahara, Kazuo

AU - Sasaki, Yasutsuna

AU - Takahashi, Terumi

AU - Saijo, Nagahiro

PY - 1990/8/1

Y1 - 1990/8/1

N2 - The mechanism of action of 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) was examined in a human leukemia cell line (K562) and its Adriamycin (ADM)-resistant subline (K562/ADM). ADM and MX2 showed an equivalent antitumor effect against K562. K562/ADM was highly resistant to ADM. In cellular pharmacokinetic studies, MX2 showed faster and greater influx than did ADM in both K562 and K562/ADM. The efflux of ADM was rapid in K562/ADM but not in K562. On the other hand, the efflux of MX2 was rapid in both cell lines. The formation of DNA single-strand breaks and double-strand breaks by ADM was significantly lower in K562/ADM than K562. On the other hand, formation of those breaks by MX2 was not decreased. Although some of the DNA breaks induced by MX2 were resealed, there was no difference in the degree of resealing in K562 and K562/ADM cells. On the other hand, most of the small number of DNA breaks in K562/ADM induced by ADM were resealed. The topoisomerase II activity in K562 and K562/ADM was not significantly different. It is concluded that MX2 conquers multidrug resistance by rapid influx following a higher frequency of formation of DNA single- and double-strand breaks in K562/ADM cells.

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