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 language | English (US) |
|---|---|
| Pages (from-to) | 123-134 |
| Number of pages | 12 |
| Journal | Cancer Letters |
| Volume | 240 |
| Issue number | 1 |
| DOIs | |
| State | Published - Aug 18 2006 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Resveratrol-induced apoptosis is enhanced in acute lymphoblastic leukemia cells by modulation of the mitochondrial permeability transition pore
AU - Zunino, Susan J.
AU - Storms, David H.
PY - 2006/8/18
Y1 - 2006/8/18
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cyclosporin A
KW - Leukemia
KW - PK11195
KW - Resveratrol
UR - http://www.scopus.com/inward/record.url?scp=33745808321&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745808321&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2005.09.001
DO - 10.1016/j.canlet.2005.09.001
M3 - Article
C2 - 16226372
AN - SCOPUS:33745808321
VL - 240
SP - 123
EP - 134
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -