Amiloride potentiates TRAIL-induced tumor cell apoptosis by intracellular acidification-dependent Akt inactivation

Young Lai Cho, Kwang Soon Lee, Seon Jin Lee, Seung Namkoong, Young Mi Kim, Hansoo Lee, Kwon Soo Ha, Jeong A. Han, Young-Guen Kwon, Young Myeong Kim

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor gene family, is considered as one of the most promising cancer therapeutic agents due to its ability to selectively induce tumor cell apoptosis. In this study, we investigated whether the Na +/H+ exchanger inhibitor, amiloride, promotes TRAIL-induced apoptotic death both in sensitive and resistant tumor cells, HeLa and LNCaP cells, respectively, and its underlying molecular mechanism. Amiloride enhanced TRAIL-induced apoptosis and activation of caspase-3 and -8 in both cells. This compound increased TRAIL-induced mitochondrial cytochrome c release and poly(ADP-ribose) polymerase cleavage. Moreover, amiloride-induced intracellular acidification, and inhibited the phosphorylated activation of the serine/threonine kinase Akt, which is known to promote cell survival, in both tumor cells. These data suggest that amiloride sensitizes both tumor cells to TRAIL-induced apoptosis by promoting Akt dephosphorylation and caspase-8 activation via the intracellular acidification and that Na+/H + exchanger inhibitors may play an important role in the anti-cancer activity of TRAIL, especially, in TRAIL-resistant tumors with highly active and expressed Akt.

Original languageEnglish
Pages (from-to)752-758
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume326
Issue number4
DOIs
Publication statusPublished - 2005 Jan 28

Fingerprint

Acidification
Amiloride
Tumors
Cells
Apoptosis
Sodium-Hydrogen Antiporter
Chemical activation
Neoplasms
Caspase 8
Tumor Necrosis Factor-alpha
Poly(ADP-ribose) Polymerases
Protein-Serine-Threonine Kinases
Cytochromes c
Caspase 3
Genes
HeLa Cells
Ligands
Cell Survival

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cho, Young Lai ; Lee, Kwang Soon ; Lee, Seon Jin ; Namkoong, Seung ; Kim, Young Mi ; Lee, Hansoo ; Ha, Kwon Soo ; Han, Jeong A. ; Kwon, Young-Guen ; Kim, Young Myeong. / Amiloride potentiates TRAIL-induced tumor cell apoptosis by intracellular acidification-dependent Akt inactivation. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 326, No. 4. pp. 752-758.
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Amiloride potentiates TRAIL-induced tumor cell apoptosis by intracellular acidification-dependent Akt inactivation. / Cho, Young Lai; Lee, Kwang Soon; Lee, Seon Jin; Namkoong, Seung; Kim, Young Mi; Lee, Hansoo; Ha, Kwon Soo; Han, Jeong A.; Kwon, Young-Guen; Kim, Young Myeong.

In: Biochemical and Biophysical Research Communications, Vol. 326, No. 4, 28.01.2005, p. 752-758.

Research output: Contribution to journalArticle

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AU - Kim, Young Mi

AU - Lee, Hansoo

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AU - Kwon, Young-Guen

AU - Kim, Young Myeong

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