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  1. 教員研究業績
  2. 薬化学研究室
  1. 教員研究業績
  2. 薬化学研究室
  3. 原著論文

Elucidating the rapid action of 2-(2-chlorophenyl)ethylbiguanide on HT-29 cells under a serum- and glucose-deprived condition

https://gifu-pu.repo.nii.ac.jp/records/13455
https://gifu-pu.repo.nii.ac.jp/records/13455
2ffbfb8f-6cae-46ae-84b6-0c1ac4b0046f
Item type 会議発表論文 / Conference Paper(1)
公開日 2019-03-04
タイトル
言語 en
タイトル Elucidating the rapid action of 2-(2-chlorophenyl)ethylbiguanide on HT-29 cells under a serum- and glucose-deprived condition
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_5794
資源タイプ conference paper
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Oh-hashi, Kentaro

× Oh-hashi, Kentaro

WEKO 21783

Oh-hashi, Kentaro

Search repository
Matsumoto, Shiori

× Matsumoto, Shiori

WEKO 21784

Matsumoto, Shiori

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Sakai, Takayuki

× Sakai, Takayuki

WEKO 21785

Sakai, Takayuki

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Nomura, Yuki

× Nomura, Yuki

WEKO 21786

Nomura, Yuki

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Okuda, Kensuke

× Okuda, Kensuke

WEKO 21787

Okuda, Kensuke

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Nagasawa, Hideko

× Nagasawa, Hideko

WEKO 21788

Nagasawa, Hideko

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Hirata, Yoko

× Hirata, Yoko

WEKO 21789

Hirata, Yoko

Search repository
抄録
内容記述タイプ Abstract
内容記述 We recently demonstrated the cytotoxic action of a novel phenformin derivative, 2-(2-chlorophenyl)ethylbiguanide (2-Cl-Phen), on HT-29 cells under a serum- and glucose-deprived condition. In that study, we showed that the ATF6 arm of the ER stress pathway and c-Myc expression were downregulated 12 h after the treatment with 2-Cl-Phen. Through characterization of intracellular events at the early phase of the 2-Cl-Phen treatment before noticeable morphological changes, we found rapid fluctuations in the c-Myc and ATF4 proteins but not in their mRNAs in 2-Cl-Phen-treated HT-29 cells under the serum- and glucose-deprived condition. The 2-Cl-Phen-mediated downregulation of ATF4 protein was not paralleled by the phosphorylation status of PERK and eIF2α. Reduction of c-Myc expression by 2-Cl-Phen was more profound than that of ATF4 expression, and phosphorylated c-Myc was downregulated within 2 h. Pharmacological studies on the expression of c-Myc and ATF4 proteins showed that this decrease was mediated through proteasomal degradation but not by autophagy. Interestingly, treatment with lithium chloride, which is a well-known inhibitor of GSK3β, partially recovered the expression of ATF4 protein, but its effect on the level of total c-Myc protein was negligible. Treatment with 2-Cl-Phen increased the expression of phosphorylated AMPK, but Compound C, an AMPK inhibitor, did not influence the expression of c-Myc protein in HT-29 cells. Finally, we observed that 2-Cl-Phen partially attenuated the gene expression of integrin subunit α1 (ITGA1), a downstream target of c-Myc. Taken together, these results show that 2-Cl-Phen rapidly downregulated the expression of c-Myc in addition to ER stress responses in a post-translational manner. Further elucidation and improvement of this multi-target-directed compound will provide new insights for developing therapeutic strategies against cancer.
書誌情報 en : Cell Biology and Toxicology

巻 34, 号 4, p. 279-290, 発行日 2017
ISSN
収録物識別子タイプ ISSN
収録物識別子 0742-2091
DOI
識別子タイプ DOI
関連識別子 10.1007/s10565-017-9410-0
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