Sulindac sulfide alters the expression of cyclin proteins in HT-29 colon adenocarcinoma cells.
Sulindac sulfide (SS), the active metabolite of the colon cancer chemopreventive compound sulindac, inhibits the proliferation of HT-29 colon cancer cells mainly by inducing cell quiescence. We determined by bivariate flow-cytometric analysis both the DNA and cyclin protein content of individual cells. Thus, we assessed in detail the expression of several cyclins during the cell-cycle phases and demonstrated that SS (i) decreases the expression of cyclins B1 and E and (ii) increases the expression of cyclins D1, D2 and D3, particularly in the G1 phase of the cell cycle. SS-induced apoptotic cells expressed both E- and D-type cyclins but not cyclin B1. The changes in cyclin expression combined with reduced catalytic activity of cyclin-dependent kinases could explain in molecular terms the anti-proliferative effect of SS on HT-29 colon cancer cells. These changes may contribute to the chemopreventive effect of sulindac.
Qiao
L
L
Department of Medicine, New York Methodist Hospital, Brooklyn, USA.
Shiff
S J
SJ
Rigas
B
B
D000230:Adenocarcinoma / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D019938:Cyclin D1 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D016213:Cyclins; D019938:Cyclin D1; D013467:Sulindac; C025462:sulindac sulfide