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Title: Apoptosis and inactivation of the PI3-kinase pathway by tetrocarcin A in breast cancers

Abstract

A survival kinase, Akt, is a downstream factor in the phosphatidylinositide-3'-kinase-dependent pathway, which mediates many biological responses including glucose uptake, protein synthesis and the regulation of proliferation and apoptosis, which is assumed to contribute to acquisition of malignant properties of human cancers. Here we find that an anti-tumor antibiotic, tetrocarcin A, directly induces apoptosis of human breast cancer cells. The apoptosis is accompanied by the activation of a proteolytic cascade of caspases including caspase-3 and -9, and concomitantly decreases phosphorylation of Akt, PDK1, and PTEN, a tumor suppressor that regulates the activity of Akt through the dephosphorylation of polyphosphoinositides. Tetrocarcin A affected neither expression of Akt, PDK1, or PTEN, nor did it affect the expression of Bcl family members including Bcl-2, Bcl-X{sub L}, and Bax. These results suggest that tetrocarcin A could be a potent chemotherapeutic agent for human breast cancer targeting the phosphatidylinositide-3'-kinase/Akt signaling pathway.

Authors:
 [1];  [1];  [1];  [1];  [2];  [3];  [1]
  1. Department of Endocrine and Breast Surgery, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamikyo-ku, Kyoto 602-0841 (Japan)
  2. Department of Biotechnology, Institute of Research and Innovation, 1201 Takada, Kashiwa 227-0861 (Japan)
  3. Department of Biotechnology, Institute of Research and Innovation, 1201 Takada, Kashiwa 227-0861 (Japan). E-mail: jmagae@sannet.ne.jp
Publication Date:
OSTI Identifier:
20991317
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 356; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2007.02.136; PII: S0006-291X(07)00425-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANTIBIOTICS; APOPTOSIS; BIOSYNTHESIS; BORON CHLORIDES; CARCINOMAS; CELL PROLIFERATION; GENE REGULATION; GLUCOSE; INACTIVATION; MAMMARY GLANDS; PHOSPHORYLATION; PROTEINS; UPTAKE

Citation Formats

Nakajima, Hiroo, Sakaguchi, Koichi, Fujiwara, Ikuya, Mizuta, Mitsuhiko, Tsuruga, Mie, Magae, Junji, and Mizuta, Naruhiko. Apoptosis and inactivation of the PI3-kinase pathway by tetrocarcin A in breast cancers. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.02.136.
Nakajima, Hiroo, Sakaguchi, Koichi, Fujiwara, Ikuya, Mizuta, Mitsuhiko, Tsuruga, Mie, Magae, Junji, & Mizuta, Naruhiko. Apoptosis and inactivation of the PI3-kinase pathway by tetrocarcin A in breast cancers. United States. doi:10.1016/j.bbrc.2007.02.136.
Nakajima, Hiroo, Sakaguchi, Koichi, Fujiwara, Ikuya, Mizuta, Mitsuhiko, Tsuruga, Mie, Magae, Junji, and Mizuta, Naruhiko. Fri . "Apoptosis and inactivation of the PI3-kinase pathway by tetrocarcin A in breast cancers". United States. doi:10.1016/j.bbrc.2007.02.136.
@article{osti_20991317,
title = {Apoptosis and inactivation of the PI3-kinase pathway by tetrocarcin A in breast cancers},
author = {Nakajima, Hiroo and Sakaguchi, Koichi and Fujiwara, Ikuya and Mizuta, Mitsuhiko and Tsuruga, Mie and Magae, Junji and Mizuta, Naruhiko},
abstractNote = {A survival kinase, Akt, is a downstream factor in the phosphatidylinositide-3'-kinase-dependent pathway, which mediates many biological responses including glucose uptake, protein synthesis and the regulation of proliferation and apoptosis, which is assumed to contribute to acquisition of malignant properties of human cancers. Here we find that an anti-tumor antibiotic, tetrocarcin A, directly induces apoptosis of human breast cancer cells. The apoptosis is accompanied by the activation of a proteolytic cascade of caspases including caspase-3 and -9, and concomitantly decreases phosphorylation of Akt, PDK1, and PTEN, a tumor suppressor that regulates the activity of Akt through the dephosphorylation of polyphosphoinositides. Tetrocarcin A affected neither expression of Akt, PDK1, or PTEN, nor did it affect the expression of Bcl family members including Bcl-2, Bcl-X{sub L}, and Bax. These results suggest that tetrocarcin A could be a potent chemotherapeutic agent for human breast cancer targeting the phosphatidylinositide-3'-kinase/Akt signaling pathway.},
doi = {10.1016/j.bbrc.2007.02.136},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 356,
place = {United States},
year = {Fri Apr 27 00:00:00 EDT 2007},
month = {Fri Apr 27 00:00:00 EDT 2007}
}