Sulindac sulfide alters the expression of cyclin proteins in HT-29 colon adenocarcinoma cells

Int J Cancer. 1998 Mar 30;76(1):99-104. doi: 10.1002/(sici)1097-0215(19980330)76:1<99::aid-ijc16>;2-b.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Cycle
  • Cell Division / drug effects
  • Colonic Neoplasms / metabolism*
  • Cyclin B / metabolism
  • Cyclin B1
  • Cyclin D1 / metabolism
  • Cyclins / metabolism*
  • HT29 Cells
  • Humans
  • Sulindac / analogs & derivatives*
  • Sulindac / pharmacology


  • Antineoplastic Agents
  • CCNB1 protein, human
  • Cyclin B
  • Cyclin B1
  • Cyclins
  • Cyclin D1
  • Sulindac
  • sulindac sulfide