TY - JOUR
T1 - Atorvastatin induces apoptosis in vitro and slows growth of tumor xenografts but not polyp formation in min mice
AU - Huang, Emina H.
AU - Johnson, Laura A.
AU - Eaton, Kathryn
AU - Hynes, Mark J.
AU - Carpentino, Joseph E.
AU - Higgins, Peter D.R.
N1 - Funding Information:
Acknowledgments We are grateful to Duyen Dang, MD and John Kao, MD, for careful reading of the manuscript. We acknowledge Marda Jorgenson and the Cells and Tissue Analysis Core at the University of Florida for the TUNEL staining. EHH was supported by NCI K08 91975 and is currently supported by the Eli and Edythe Broad Foundation. JEC is supported by the Regeneration Project (University of Florida) and the Broad Foundation.
PY - 2010/11
Y1 - 2010/11
N2 - Background: Despite the availability of effective surveillance for colorectal cancer with colonoscopy, relatively few at-risk individuals utilize this option. Colon cancer chemoprevention might be a more acceptable alternative. Some epidemiologic studies have suggested that statins may have chemopreventive effects without the risks of nonsteroidal anti-inflammatory drugs, but other epidemiologic studies have found no effect of statins. Methods: We aimed to evaluate the efficacy of atorvastatin in inducing apoptosis in vitro, in preventing polyp formation in the min mouse, and in preventing tumor growth in nude mice. Results: Atorvastatin rapidly induces apoptosis in the HCT116 colon cancer cell line in vitro, and this effect is reversible with mevalonate and geranylgeranyl pyrophosphate, but less so by farnesyl pyrophosphate. Atorvastatin chow was ineffective in reducing polyp formation in the min mouse model, with no significant effect on polyp number. Atorvastatin was effective in significantly slowing the growth of HCT116 colon cancer cell xenografts in nude mice (p = 0.008). Further, this reduction is due to increased levels of apoptosis. Conclusions: Atorvastatin can induce apoptosis in vitro, through mevalonate and prenylation pathways. Atorvastatin, while not effective in preventing polyp formation in the min mouse model, was very effective in slowing tumor growth in a nude mouse model. Consistent with in vitro findings, increased apoptosis accounted for decreased tumor growth. Statins may have benefit in cancer by slowing tumor growth, rather than preventing tumor initiation.
AB - Background: Despite the availability of effective surveillance for colorectal cancer with colonoscopy, relatively few at-risk individuals utilize this option. Colon cancer chemoprevention might be a more acceptable alternative. Some epidemiologic studies have suggested that statins may have chemopreventive effects without the risks of nonsteroidal anti-inflammatory drugs, but other epidemiologic studies have found no effect of statins. Methods: We aimed to evaluate the efficacy of atorvastatin in inducing apoptosis in vitro, in preventing polyp formation in the min mouse, and in preventing tumor growth in nude mice. Results: Atorvastatin rapidly induces apoptosis in the HCT116 colon cancer cell line in vitro, and this effect is reversible with mevalonate and geranylgeranyl pyrophosphate, but less so by farnesyl pyrophosphate. Atorvastatin chow was ineffective in reducing polyp formation in the min mouse model, with no significant effect on polyp number. Atorvastatin was effective in significantly slowing the growth of HCT116 colon cancer cell xenografts in nude mice (p = 0.008). Further, this reduction is due to increased levels of apoptosis. Conclusions: Atorvastatin can induce apoptosis in vitro, through mevalonate and prenylation pathways. Atorvastatin, while not effective in preventing polyp formation in the min mouse model, was very effective in slowing tumor growth in a nude mouse model. Consistent with in vitro findings, increased apoptosis accounted for decreased tumor growth. Statins may have benefit in cancer by slowing tumor growth, rather than preventing tumor initiation.
KW - Apoptosis
KW - Chemoprevention
KW - Colon cancer
KW - Statins
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U2 - 10.1007/s10620-010-1157-x
DO - 10.1007/s10620-010-1157-x
M3 - Article
C2 - 20186482
AN - SCOPUS:78149357224
SN - 0163-2116
VL - 55
SP - 3086
EP - 3094
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 11
ER -