Diindolylmethane (DIM) spontaneously forms from indole-3-carbinol (I3C) during cell culture experiments

In Vivo. 2010 Jul-Aug;24(4):387-91.


Indole-3-carbinol (I3C) when given orally is converted to diindolylmethane (DIM) and other oligomers catalyzed by stomach acid. This suggests that DIM is the predominant active agent and that I3C is a precursor, 'pro-drug' in vivo. However, in cell culture studies carried out in neutral solutions, I3C has been considered fully active.

Materials and methods: The stability of I3C in cell culture media was studied.

Results: In the 8 different cell culture media tested, greater than 50% dimerization of I3C into DIM occurred in 24 hours. At 48 hour, greater than 60% conversion was found. When neutral synthetic cerebrospinal fluid (CSF) or peritoneal fluid (PF) was studied, a large peak, tentitively identified as I3C's linear trimer (LTR) conversion product by mass spectra, and two smaller peaks, were seen. When CSF or PF was diluted 1:1 with media, the formation of these additional peaks was diminished.

Conclusion: Because of the greater biologic potency of DIM when studied in parallel with I3C in vitro, this extent of dimerization shows that DIM rather than I3C is the active agent in cell culture studies.

MeSH terms

  • Animals
  • Biotransformation
  • Breast Neoplasms / metabolism
  • Calibration
  • Cell Culture Techniques / methods
  • Culture Media
  • Dimerization
  • Female
  • Gastric Acid / metabolism
  • Humans
  • Indoles / metabolism*
  • Male
  • Prodrugs / metabolism
  • Prostatic Neoplasms / metabolism
  • Species Specificity
  • Uterine Cervical Neoplasms / metabolism


  • Culture Media
  • Indoles
  • Prodrugs
  • indole-3-carbinol
  • 3,3'-diindolylmethane