Open Access

LW6, a hypoxia‑inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells

  • Authors:
    • Mariko Sato
    • Katsumi Hirose
    • Ikuo Kashiwakura
    • Masahiko Aoki
    • Hideo Kawaguchi
    • Yoshiomi Hatayama
    • Hiroyoshi Akimoto
    • Yuichiro Narita
    • Yoshihiro Takai
  • View Affiliations

  • Published online on: May 27, 2015     https://doi.org/10.3892/mmr.2015.3862
  • Pages: 3462-3468
  • Copyright: © Sato et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Hypoxia‑inducible factor 1 (HIF‑1) activates the transcription of genes that act upon the adaptation of cancer cells to hypoxia. LW6, an HIF‑1 inhibitor, was hypothesized to improve resistance to cancer therapy in hypoxic tumors by inhibiting the accumulation of HIF‑1α. A clear anti‑tumor effect under low oxygen conditions would indicate that LW6 may be an improved treatment strategy for cancer in hypoxia. In the present study, the HIF‑1 inhibition potential of LW6 on the growth and apoptosis of A549 lung cancer cells in association with oxygen availability was evaluated. LW6 was observed to inhibit the expression of HIF‑1α induced by hypoxia in A549 cells at 20 mM, independently of the von Hippel‑Lindau protein. In addition, at this concentration, LW6 induced hypoxia‑selective apoptosis together with a reduction in the mitochondrial membrane potential. The intracellular reactive oxygen species levels increased in LW6‑treated hypoxic A549 cells and LW6 induced a hypoxia‑selective increase of mitochondrial O2•‑. In conclusion, LW6 inhibited the growth of hypoxic A549 cells by affecting the mitochondria. The inhibition of the mitochondrial respiratory chain is suggested as a potentially effective strategy to target apoptosis in cancer cells.
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September-2015
Volume 12 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Sato M, Hirose K, Kashiwakura I, Aoki M, Kawaguchi H, Hatayama Y, Akimoto H, Narita Y and Takai Y: LW6, a hypoxia‑inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells. Mol Med Rep 12: 3462-3468, 2015
APA
Sato, M., Hirose, K., Kashiwakura, I., Aoki, M., Kawaguchi, H., Hatayama, Y. ... Takai, Y. (2015). LW6, a hypoxia‑inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells. Molecular Medicine Reports, 12, 3462-3468. https://doi.org/10.3892/mmr.2015.3862
MLA
Sato, M., Hirose, K., Kashiwakura, I., Aoki, M., Kawaguchi, H., Hatayama, Y., Akimoto, H., Narita, Y., Takai, Y."LW6, a hypoxia‑inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells". Molecular Medicine Reports 12.3 (2015): 3462-3468.
Chicago
Sato, M., Hirose, K., Kashiwakura, I., Aoki, M., Kawaguchi, H., Hatayama, Y., Akimoto, H., Narita, Y., Takai, Y."LW6, a hypoxia‑inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells". Molecular Medicine Reports 12, no. 3 (2015): 3462-3468. https://doi.org/10.3892/mmr.2015.3862