Resveratrol-induced apoptosis is enhanced in acute lymphoblastic leukemia cells by modulation of the mitochondrial permeability transition pore

Susan J. Zunino, David H. Storms

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

We have previously shown that resveratrol can induce apoptotic cell death in cell lines established from patients with acute lymphoblastic leukemia (ALL). Cyclosporin A (CsA) and PK11195 are modulators of the mitochondrial permeability transition pore (MPTP) which has been proposed to play a critical role in regulating survival and death. Using SEM and RS4;11 lines with the t(4;11) translocation, the B-ALL line REH, and the T-ALL line Jurkat, we show that pre-treatment with CsA or PK11195 significantly enhances resveratrol-mediated apoptosis and mitochondrial membrane depolarization in these cells, as measured by annexin V and JC-1 staining, respectively. No significant multi-drug resistance efflux of the fluorescent substrate calcein was observed in these ALL lines, indicating that CsA and PK11195 were acting at the level of the mitochondria to enhance loss of mitochondrial membrane potential and induction of apoptosis. These data suggest targeting the MPTP sensitizes B- and T-cell ALL to the anti-cancer activity of resveratrol, and may be particularly useful for the treatment of high-risk t(4;11) ALL.

Original languageEnglish (US)
Pages (from-to)123-134
Number of pages12
JournalCancer Letters
Volume240
Issue number1
DOIs
StatePublished - Aug 18 2006
Externally publishedYes

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Apoptosis
Cyclosporine
Biphenotypic Acute Leukemia
Mitochondrial Membrane Potential
Annexin A5
Mitochondrial Membranes
Multiple Drug Resistance
Mitochondria
Cell Death
resveratrol
mitochondrial permeability transition pore
Staining and Labeling
Cell Line
Survival
Therapeutics
PK 11195
Neoplasms

Keywords

  • Apoptosis
  • Cyclosporin A
  • Leukemia
  • PK11195
  • Resveratrol

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Resveratrol-induced apoptosis is enhanced in acute lymphoblastic leukemia cells by modulation of the mitochondrial permeability transition pore. / Zunino, Susan J.; Storms, David H.

In: Cancer Letters, Vol. 240, No. 1, 18.08.2006, p. 123-134.

Research output: Contribution to journalArticle

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