Deguelin inhibits the growth of colon cancer cells through the induction of apoptosis and cell cycle arrest

Eur J Cancer. 2002 Dec;38(18):2446-54. doi: 10.1016/s0959-8049(02)00192-2.


As previously demonstrated, deguelin [(7aS, BaS)-13, 13a-dihydro-9,10-dimethoxy-3,3-dimethyl-3H-bis[1]benzo-pyrano[3,4-b:6',5'-e]pyran-7(7aH)-one mediates anti-proliferative properties in a variety of cell types. In the present study, deguelin was found to suppress the growth of HT-29 colon cancer cells with an IC(50) of 4.32 x 10(-8) M. The cells were arrested in the G1-S-phase of the cycle. Investigations of G1/S regulatory proteins by Western blot analyses showed an upregulation of p27, and decreased expression levels of cyclin E and CDK4. Furthermore, by 24 h, exposure to deguelin resulted in an increase in the hypophosphorylated form of Rb. Since hypophosphorylated pRb binds to and inactivates E2F1, additional studies were performed and downregulation of E2F1 was observed after 24 h of treatment with deguelin. These results are consistent with the observation that deguelin arrested cells in the G1-S- phase. In addition, based on ethidium bromide/acridine orange staining, detection of digoxigenin-labelled genomic 3'-OH DNA ends, and DNA laddering, it was found that deguelin exerts its growth inhibitory effects via the induction of apoptosis. Based on these data, the potential of deguelin to serve as a cancer chemotherapeutic agent for colon cancer may be suggested.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Apoptosis*
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Cyclin-Dependent Kinases / drug effects
  • Cyclin-Dependent Kinases / metabolism
  • HT29 Cells / drug effects
  • Humans
  • Microfilament Proteins / drug effects
  • Microfilament Proteins / metabolism
  • Muscle Proteins*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Retinoblastoma Protein / drug effects
  • Retinoblastoma Protein / metabolism
  • Rotenone / analogs & derivatives*
  • Rotenone / therapeutic use*
  • Tumor Cells, Cultured
  • Up-Regulation


  • Antineoplastic Agents
  • Microfilament Proteins
  • Muscle Proteins
  • Proliferating Cell Nuclear Antigen
  • Retinoblastoma Protein
  • Tagln protein, mouse
  • Rotenone
  • Cyclin-Dependent Kinases
  • deguelin