Growth compensatory role of sulindac sulfide-induced thrombospondin-1 linked with ERK1/2 and RhoA GTPase signaling pathways.
Previously, we reported that non-steroidal anti-inflammatory drugs (NSAIDs) suppress cellular invasion which was mediated by thrombospondin-1 (TSP-1). As the extending study of the previous observation, we investigated the effect of NSAID-induced TSP-1 on the cellular growth and its related signaling transduction of the TSP-1 production. Among diverse NSAIDs, sulindac sulfide was most potent of inducing the human TSP-1 protein expression. Functionally, induced TSP-1 expression was associated with the growth-compensatory action of NSAID. TSP-1 expression was also elevated by mitogenic signals of ERK1/2 and RhoA GTPase pathway which had also growth-promotive capability after sulindac sulfide treatment. These findings suggest the possible mechanism through which tumor cells can survive the chemopreventive action of NSAIDs or the normal epithelium can reconstitute after NSAID-mediated ulceration in a compensatory way.
Moon
Yuseok
Y
Department of Microbiology and Immunology and Medical Research Institute, Pusan National University School of Medicine, Busan, 602-739, Republic of Korea. moon@pusan.ac.kr
Kim
Jeung Il
JI
Yang
Hyun
H
Eling
Thomas E
TE
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000378:metabolism; D007213:Indomethacin / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013467:Sulindac / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019700:Thrombospondin 1; D013467:Sulindac; C025462:sulindac sulfide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020742:rhoA GTP-Binding Protein; D007052:Ibuprofen; D007213:Indomethacin