Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10

Takuya Yokoyama, Masaki Yukuhiro, Yuka Iwasaki, Chika Tanaka, Kazunari Sankoda, Risa Fujiwara, Atsushi Shibuta, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima, Kazumasa Yoshida, Nozomi Sugimoto, Hiroyuki Morimoto, Hidetaka Kosako, Takashi Ohshima, Masatoshi Fujita

研究成果: ジャーナルへの寄稿記事

抄録

We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents.

元の言語英語
記事番号16825
ジャーナルScientific reports
9
発行部数1
DOI
出版物ステータス出版済み - 12 1 2019

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Antimitotic Agents
Antineoplastic Agents
polyoxyethylene(10)nonylphenyl ether
Karyopherins
HCT116 Cells
HeLa Cells
Mitosis
Nude Mice
Mass Spectrometry
Neoplasms
Body Weight

All Science Journal Classification (ASJC) codes

  • General

これを引用

Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10. / Yokoyama, Takuya; Yukuhiro, Masaki; Iwasaki, Yuka; Tanaka, Chika; Sankoda, Kazunari; Fujiwara, Risa; Shibuta, Atsushi; Higashi, Taishi; Motoyama, Keiichi; Arima, Hidetoshi; Yoshida, Kazumasa; Sugimoto, Nozomi; Morimoto, Hiroyuki; Kosako, Hidetaka; Ohshima, Takashi; Fujita, Masatoshi.

:: Scientific reports, 巻 9, 番号 1, 16825, 01.12.2019.

研究成果: ジャーナルへの寄稿記事

Yokoyama, T, Yukuhiro, M, Iwasaki, Y, Tanaka, C, Sankoda, K, Fujiwara, R, Shibuta, A, Higashi, T, Motoyama, K, Arima, H, Yoshida, K, Sugimoto, N, Morimoto, H, Kosako, H, Ohshima, T & Fujita, M 2019, 'Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10', Scientific reports, 巻. 9, 番号 1, 16825. https://doi.org/10.1038/s41598-019-53259-2
Yokoyama T, Yukuhiro M, Iwasaki Y, Tanaka C, Sankoda K, Fujiwara R その他. Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10. Scientific reports. 2019 12 1;9(1). 16825. https://doi.org/10.1038/s41598-019-53259-2
Yokoyama, Takuya ; Yukuhiro, Masaki ; Iwasaki, Yuka ; Tanaka, Chika ; Sankoda, Kazunari ; Fujiwara, Risa ; Shibuta, Atsushi ; Higashi, Taishi ; Motoyama, Keiichi ; Arima, Hidetoshi ; Yoshida, Kazumasa ; Sugimoto, Nozomi ; Morimoto, Hiroyuki ; Kosako, Hidetaka ; Ohshima, Takashi ; Fujita, Masatoshi. / Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10. :: Scientific reports. 2019 ; 巻 9, 番号 1.
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abstract = "We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents.",
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AU - Sankoda, Kazunari

AU - Fujiwara, Risa

AU - Shibuta, Atsushi

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AU - Motoyama, Keiichi

AU - Arima, Hidetoshi

AU - Yoshida, Kazumasa

AU - Sugimoto, Nozomi

AU - Morimoto, Hiroyuki

AU - Kosako, Hidetaka

AU - Ohshima, Takashi

AU - Fujita, Masatoshi

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