Abstract
ApcMin mice are widely used for mechanism and efficacy studies associated with the development of chemopreventive agents. APC10.1 cells have been derived from ApcMin mouse adenomas and retain the heterozygous Apc genotype. We tested the hypothesis that this cell type may provide an in vitro model to predict chemopreventive activity of agents in the ApcMin mouse in vivo. The growth inhibitory properties of 14 putative colorectal cancer chemopreventive agents, tricin, apigenin, 3′,4′,5′,5,7-pentamethoxyflavone, resveratrol, curcumin, 3,4-methylenedioxy-3′,4′,5′-trimethoxychalcone (DMU135), 3,4,5,4′-tetramethoxystilbene (DMU212), celecoxib, aspirin, piroxicam, all-trans-retinoic acid, difluoromethylornithine (DFMO), quercetin and cyanidin-3-glucoside, were studied in this cell line, and the IC50 values were calculated. The IC50 values were plotted against previously published data of reduction of adenoma numbers caused by these agents in ApcMin mice. The correlation co-efficient was 0.678 (p <0.01), suggesting that there was a tentative correlation between the ability to inhibit the growth of APC10.1 cells and the ability to delay adenoma development in vivo. If this relationship is supported by using further agents, APC10.1 cells may serve in the future as an initial screen to prioritise compounds for assessing chemopreventive efficacy in ApcMin mice in vivo. Such a screen could reduce the number of animals required to find active agents, help reduce costs and increase throughput.
| Original language | English |
|---|---|
| Pages (from-to) | 2731-2735 |
| Number of pages | 5 |
| Journal | European Journal of Cancer |
| Volume | 45 |
| Issue number | 16 |
| DOIs | |
| Publication status | Published - Nov 2009 |
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Keywords
- APC10.1
- Apc mouse
- Chemoprevention
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
APC10.1 cells as a model for assessing the efficacy of potential chemopreventive agents in the ApcMin mouse model in vivo. / Sale, Stewart; Fong, Isabel L.; de Giovanni, Carla; Landuzzi, Lorena; Brown, Karen; Steward, William P.; Gescher, Andreas J.
In: European Journal of Cancer, Vol. 45, No. 16, 11.2009, p. 2731-2735.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - APC10.1 cells as a model for assessing the efficacy of potential chemopreventive agents in the ApcMin mouse model in vivo
AU - Sale, Stewart
AU - Fong, Isabel L.
AU - de Giovanni, Carla
AU - Landuzzi, Lorena
AU - Brown, Karen
AU - Steward, William P.
AU - Gescher, Andreas J.
PY - 2009/11
Y1 - 2009/11
N2 - ApcMin mice are widely used for mechanism and efficacy studies associated with the development of chemopreventive agents. APC10.1 cells have been derived from ApcMin mouse adenomas and retain the heterozygous Apc genotype. We tested the hypothesis that this cell type may provide an in vitro model to predict chemopreventive activity of agents in the ApcMin mouse in vivo. The growth inhibitory properties of 14 putative colorectal cancer chemopreventive agents, tricin, apigenin, 3′,4′,5′,5,7-pentamethoxyflavone, resveratrol, curcumin, 3,4-methylenedioxy-3′,4′,5′-trimethoxychalcone (DMU135), 3,4,5,4′-tetramethoxystilbene (DMU212), celecoxib, aspirin, piroxicam, all-trans-retinoic acid, difluoromethylornithine (DFMO), quercetin and cyanidin-3-glucoside, were studied in this cell line, and the IC50 values were calculated. The IC50 values were plotted against previously published data of reduction of adenoma numbers caused by these agents in ApcMin mice. The correlation co-efficient was 0.678 (p <0.01), suggesting that there was a tentative correlation between the ability to inhibit the growth of APC10.1 cells and the ability to delay adenoma development in vivo. If this relationship is supported by using further agents, APC10.1 cells may serve in the future as an initial screen to prioritise compounds for assessing chemopreventive efficacy in ApcMin mice in vivo. Such a screen could reduce the number of animals required to find active agents, help reduce costs and increase throughput.
AB - ApcMin mice are widely used for mechanism and efficacy studies associated with the development of chemopreventive agents. APC10.1 cells have been derived from ApcMin mouse adenomas and retain the heterozygous Apc genotype. We tested the hypothesis that this cell type may provide an in vitro model to predict chemopreventive activity of agents in the ApcMin mouse in vivo. The growth inhibitory properties of 14 putative colorectal cancer chemopreventive agents, tricin, apigenin, 3′,4′,5′,5,7-pentamethoxyflavone, resveratrol, curcumin, 3,4-methylenedioxy-3′,4′,5′-trimethoxychalcone (DMU135), 3,4,5,4′-tetramethoxystilbene (DMU212), celecoxib, aspirin, piroxicam, all-trans-retinoic acid, difluoromethylornithine (DFMO), quercetin and cyanidin-3-glucoside, were studied in this cell line, and the IC50 values were calculated. The IC50 values were plotted against previously published data of reduction of adenoma numbers caused by these agents in ApcMin mice. The correlation co-efficient was 0.678 (p <0.01), suggesting that there was a tentative correlation between the ability to inhibit the growth of APC10.1 cells and the ability to delay adenoma development in vivo. If this relationship is supported by using further agents, APC10.1 cells may serve in the future as an initial screen to prioritise compounds for assessing chemopreventive efficacy in ApcMin mice in vivo. Such a screen could reduce the number of animals required to find active agents, help reduce costs and increase throughput.
KW - APC10.1
KW - Apc mouse
KW - Chemoprevention
UR - http://www.scopus.com/inward/record.url?scp=70350026889&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350026889&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2009.07.004
DO - 10.1016/j.ejca.2009.07.004
M3 - Article
C2 - 19695862
AN - SCOPUS:70350026889
VL - 45
SP - 2731
EP - 2735
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 16
ER -