dim-c-pphoch3

Description: DIM-C-pPhOCH3 is an agonist Nur77 (Nerve growth factor-induced Balpha, abbreviated as NGFI-Balpha or Nur77). Nur77 is an orphan nuclear receptor with no known endogenous ligands and was reported to be overexpressed in colon tumors compared with normal colon tissue. DIM-C-pPhOCH3 was able to decrease the survival and induce apoptosis in RKO colon cancer cells, and this was accompanied by induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein. The induction of apoptosis and TRAIL by DIM-C-pPhOCH3 was significantly inhibited by a small inhibitory RNA for Nur77 (iNur77); however, it was evident from RNA interference studies that DIM-C-pPhOCH3 also induced Nur77-independent apoptosis. Analysis of DIM-C-pPhOCH3-induced gene expression using microarrays identified several proapoptotic genes, and analysis by reverse transcription-PCR in the presence or absence of iNur77 showed that induction of programmed cell death gene 1 was Nur77 dependent, whereas induction of cystathionase and activating transcription factor 3 was Nur77 independent. DIM-C-pPhOCH3 (25 mg/kg/d) also inhibited tumor growth in athymic nude mice bearing RKO cell xenografts. These results show that DIM-C-pPhOCH3 represent a new class of anti-colon cancer drugs that act through receptor-dependent and receptor-independent pathways.

References: Cancer Res. 2007 Jan 15; 67(2):674-83.