Lactacystin augments the sulindac-induced apoptosis in HT-29 cells.
The present study was conducted to explore the potential role of proteasome pathway in NSAIDs-induced apoptosis. We employed sulindac as a NSAID, and chose the lactacystin for inhibition of proteasome activity. Assessment of apoptosis and proteasome activity assay were undertaken. We demonstrated that sulindac treatment resulted in a decrease of proteasome activity, and that the co-treatment of a proteasome inhibitor lactacystin potentiated the extent of sulindac-induced apoptosis in HT-29 cells by augmentation of the decrease in proteasome activity. Elucidation of the mechanism underlying the regression of colon cancers by combinations of sulindac and lactacystin seems to be an immediate challenge for the near future.
Choi
H J
HJ
Department of General Surgery, Dong-A University College of Medicine, Dongdaesin-Dong, Seo Gu, Pusan 602-714, South Korea.
Kim
H H
HH
Lee
H S
HS
Huh
G Y
GY
Seo
S Y
SY
Jeong
J H
JH
Kim
J-M
JM
Yoo
Y H
YH
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D019073:HT29 Cells; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013467:Sulindac / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; C067713:lactacystin; D013467:Sulindac; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine