Polyethylene glycol induces apoptosis in HT-29 cells: potential mechanism for chemoprevention of colon cancer.
Recent experimental evidence suggests that polyethylene glycol (PEG) is a highly effective chemopreventive agent against colon cancer; however, the mechanism(s) remain largely unexplored. To further elucidate this issue, we evaluated the effect of PEG on two human colon cancer cell lines. PEG treatment resulted in a dose- and time-dependent reduction in cell number without alteration in markers of cell proliferation. However, there was a dramatic and specific, concentration-dependent induction of apoptosis, with 50 mM PEG rendering approximately half the cells apoptotic. This corresponded with a 17-fold induction in the expression of the pro-apoptotic protein, prostate apoptosis response-4. Our data suggest that induction of apoptosis may be responsible, at least in part, for the ability of PEG to prevent experimental colon cancer.
Roy
H K
HK
Section of Gastroenterology/Hepatology, Department of Internal Medicine, University of Nebraska Medical Center/Eppley Institute for Research into Cancer and Allied Diseases, 982000 Nebraska Medical Center, Omaha, NE 68198-2000, USA. hroy@unmc.edu
DiBaise
J K
JK
Black
J
J
Karolski
W J
WJ
Ratashak
A
A
Ansari
S
S
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000517:prevention & control*; D004396:Coloring Agents / Q000494:pharmacology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D019073:HT29 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011092:Polyethylene Glycols / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D004396:Coloring Agents; D047908:Intracellular Signaling Peptides and Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C101296:prostate apoptosis response-4 protein; D011092:Polyethylene Glycols; C022616:thiazolyl blue