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Cancer Lett. 2006 Aug 18;240(1):123-34. Epub 2005 Oct 13.

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

Author information

  • 1United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, One Shields Ave., 3202A Meyer Hall, University of California, Davis, CA 95616, USA. szunino@whnrc.usda.gov <szunino@whnrc.usda.gov>

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.

PMID:
16226372
[PubMed - indexed for MEDLINE]
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