1,1-bis(3'-indolyl)-1-(p-methoxyphenyl)methane activates Nur77-independent proapoptotic responses in colon cancer cells. Academic Article uri icon


  • 1,1-Bis(3'-indolyl)-1-(p-methoxyphenyl)methane (DIM-C-pPhOCH(3)) is a methylene-substituted diindolylmethane (C-DIM) analog that activates the orphan receptor nerve growth factor-induced-Balpha (NGFI-Balpha, Nur77). RNA interference studies with small inhibitory RNA for Nur77 demonstrate that DIM-C-pPhOCH(3) induces Nur77-dependent and -independent apoptosis, and this study has focused on delineating the Nur77-independent proapoptotic pathways induced by the C-DIM analog. DIM-C-pPhOCH(3) induced caspase-dependent apoptosis in RKO colon cancer cells through decreased mitochondrial membrane potential which is accompanied by increased mitochondrial bax/bcl-2 ratios and release of cytochrome c into the cytosol. DIM-C-pPhOCH(3) also induced phosphatidylinositol-3-kinase-dependent activation of early growth response gene-1 which, in turn, induced expression of the proapoptotic nonsteroidal anti-inflammatory drug-activated gene-1 (NAG1) in RKO and SW480 colon cancer cells. Moreover, DIM-C-pPhOCH(3) also induced NAG-1 expression in colon tumors in athymic nude mice bearing RKO cells as xenografts. DIM-C-pPhOCH(3) also activated the extrinsic apoptosis pathway through increased phosphorylation of c-jun N-terminal kinase which, in turn, activated C/EBP homologous transcription factor (CHOP) and death receptor 5 (DR5). Thus, the effectiveness of DIM-C-pPhOCH(3) as a tumor growth inhibitor is through activation of Nur77-dependent and -independent pathways.

published proceedings

  • Mol Carcinog

altmetric score

  • 3

author list (cited authors)

  • Cho, S. D., Lei, P., Abdelrahim, M., Yoon, K., Liu, S., Guo, J., ... Safe, S.

citation count

  • 21

complete list of authors

  • Cho, Sung Dae||Lei, Ping||Abdelrahim, Maen||Yoon, Kyungsil||Liu, Shengxi||Guo, Jingjing||Papineni, Sabitha||Chintharlapalli, Sudhakar||Safe, Stephen

publication date

  • April 2008