Abstract
Ampelopsin A and balanocarpol were purified from Hopea dryobalanoides and their effect on sphingosine kinase 1 activity and expression, [3H] thymidine incorporation, ERK-1/2 phosphorylation and PARP activity assessed in MCF-7 cells.
Resveratrol, ampelopsin A and balanocarpol were novel inhibitors of sphingosine kinase 1 activity. Balanocarpol was a mixed inhibitor (with sphingosine) of sphingosine kinase 1 with a Kic= 90 +/- 10 mu M and a Kiu of similar to 500 mu M. Balanocarpol and ampelopsin A also induced down-regulation of sphingosine kinase 1 expression and reduced DNA synthesis, while balanocarpol stimulated PARP cleavage in MCF-7 breast cancer cells. Resveratrol was a competitive inhibitor (with sphingosine) of sphingosine kinase 1 with a Kic= 160 +/- 40 mu M, reduced sphingosine kinase 1 expression and induced PARP cleavage in MCF-7 cells.
Each molecule of balanocarpol may bind at least two sphingosine kinase 1 catalytic molecules to reduce the activity of each simultaneously. These findings suggest that resveratrol, ampelopsin A and balanocarpol could perturb sphingosine kinase 1-mediated signalling and this might explain their activity against MCF-7 breast cancer cells.
This article is commented on by Hergst and Yun, pp. 16031604 of this issue. To view this commentary visit
| Language | English |
|---|---|
| Pages | 1605-1616 |
| Number of pages | 12 |
| Journal | British Journal of Pharmacology |
| Volume | 166 |
| Issue number | 5 |
| Early online date | 21 Jun 2012 |
| DOIs | |
| Publication status | Published - Jul 2012 |
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Keywords
- resveratrol dimers
- novel sphingosine kinase 1 inhibitors
- sphingosine kinase 1 expression
- cancer cell growth
- sphingosine 1-phosphate
- ampelopsin A
- balanocarpol
- inhibitor kinetics
- polyADP ribose polymerase
- extracellular signal-regulated kinase
- resveratrol
- proliferation
- cancer
- apoptosis
- sphingosine kinase 1
Cite this
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Resveratrol dimers are novel sphingosine kinase 1 inhibitors and affect sphingosine kinase 1 expression and cancer cell growth and survival. / Lim, Keng Gat; Gray, Alexander I; Pyne, Susan; Pyne, Nigel J.
In: British Journal of Pharmacology, Vol. 166, No. 5, 07.2012, p. 1605-1616.Research output: Contribution to journal › Article
TY - JOUR
T1 - Resveratrol dimers are novel sphingosine kinase 1 inhibitors and affect sphingosine kinase 1 expression and cancer cell growth and survival
AU - Lim, Keng Gat
AU - Gray, Alexander I
AU - Pyne, Susan
AU - Pyne, Nigel J
N1 - © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
PY - 2012/7
Y1 - 2012/7
N2 - Sphingosine kinase 1 catalyses formation of the bioactive lipid, sphingosine 1-phosphate, which protects cancer cells from apoptosis. Therefore, sphingosine kinase 1 is a novel target for intervention with anti-cancer agents. We have assessed the effect of the anti-cancer agent, resveratrol and its dimers (ampelopsin A and balanocarpol) on sphingosine kinase 1 activity and on survival of MCF-7 breast cancer cells. Ampelopsin A and balanocarpol were purified from Hopea dryobalanoides and their effect on sphingosine kinase 1 activity and expression, [3H] thymidine incorporation, ERK-1/2 phosphorylation and PARP activity assessed in MCF-7 cells. Resveratrol, ampelopsin A and balanocarpol were novel inhibitors of sphingosine kinase 1 activity. Balanocarpol was a mixed inhibitor (with sphingosine) of sphingosine kinase 1 with a Kic= 90 +/- 10 mu M and a Kiu of similar to 500 mu M. Balanocarpol and ampelopsin A also induced down-regulation of sphingosine kinase 1 expression and reduced DNA synthesis, while balanocarpol stimulated PARP cleavage in MCF-7 breast cancer cells. Resveratrol was a competitive inhibitor (with sphingosine) of sphingosine kinase 1 with a Kic= 160 +/- 40 mu M, reduced sphingosine kinase 1 expression and induced PARP cleavage in MCF-7 cells. Each molecule of balanocarpol may bind at least two sphingosine kinase 1 catalytic molecules to reduce the activity of each simultaneously. These findings suggest that resveratrol, ampelopsin A and balanocarpol could perturb sphingosine kinase 1-mediated signalling and this might explain their activity against MCF-7 breast cancer cells. This article is commented on by Hergst and Yun, pp. 16031604 of this issue. To view this commentary visit
AB - Sphingosine kinase 1 catalyses formation of the bioactive lipid, sphingosine 1-phosphate, which protects cancer cells from apoptosis. Therefore, sphingosine kinase 1 is a novel target for intervention with anti-cancer agents. We have assessed the effect of the anti-cancer agent, resveratrol and its dimers (ampelopsin A and balanocarpol) on sphingosine kinase 1 activity and on survival of MCF-7 breast cancer cells. Ampelopsin A and balanocarpol were purified from Hopea dryobalanoides and their effect on sphingosine kinase 1 activity and expression, [3H] thymidine incorporation, ERK-1/2 phosphorylation and PARP activity assessed in MCF-7 cells. Resveratrol, ampelopsin A and balanocarpol were novel inhibitors of sphingosine kinase 1 activity. Balanocarpol was a mixed inhibitor (with sphingosine) of sphingosine kinase 1 with a Kic= 90 +/- 10 mu M and a Kiu of similar to 500 mu M. Balanocarpol and ampelopsin A also induced down-regulation of sphingosine kinase 1 expression and reduced DNA synthesis, while balanocarpol stimulated PARP cleavage in MCF-7 breast cancer cells. Resveratrol was a competitive inhibitor (with sphingosine) of sphingosine kinase 1 with a Kic= 160 +/- 40 mu M, reduced sphingosine kinase 1 expression and induced PARP cleavage in MCF-7 cells. Each molecule of balanocarpol may bind at least two sphingosine kinase 1 catalytic molecules to reduce the activity of each simultaneously. These findings suggest that resveratrol, ampelopsin A and balanocarpol could perturb sphingosine kinase 1-mediated signalling and this might explain their activity against MCF-7 breast cancer cells. This article is commented on by Hergst and Yun, pp. 16031604 of this issue. To view this commentary visit
KW - resveratrol dimers
KW - novel sphingosine kinase 1 inhibitors
KW - sphingosine kinase 1 expression
KW - cancer cell growth
KW - sphingosine 1-phosphate
KW - ampelopsin A
KW - balanocarpol
KW - inhibitor kinetics
KW - polyADP ribose polymerase
KW - extracellular signal-regulated kinase
KW - resveratrol
KW - proliferation
KW - cancer
KW - apoptosis
KW - sphingosine kinase 1
U2 - 10.1111/j.1476-5381.2012.01862.x
DO - 10.1111/j.1476-5381.2012.01862.x
M3 - Article
VL - 166
SP - 1605
EP - 1616
JO - British Journal of Pharmacology
T2 - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 5
ER -