Fatty acid synthase (FAS), an enzyme that is over-expressed in many cancers, is necessary for cancer cell proliferation. Previously, we have shown that FAS in cancer cells is regulated at least in part, by Sp1. Indole-3-carbinol (I3C) and its acid condensation product, 3,3’-diindolylmethane (DIM) modulate various transcription factors involved in regulating cellular proliferation and apoptosis. The objective of this study was to determine whether reductions in breast cancer cell proliferation caused by I3C and/or DIM occur as a result of reductions in FAS. DIM and, in some cases, I3C reduced FAS expression in three breast cancer cell lines. However, addition of palmitate or oleate to DIM-treated MCF-7 cells did not restore proliferation. DIM-associated reduction in proliferation of MCF-7 cells also results in a reduction of Sp1 expression, and down-regulation of FAS occurs after inhibition of proliferation. Thus, the anti-proliferative effect of I3C and DIM may be due to their effect on down-regulating Sp1, which in turn could modify several Sp1-associated genes, including FAS.

Fatty acid synthase (FAS), an enzyme that is over-expressed in many cancers, is necessary for cancer cell proliferation. Previously, we have shown that FAS in cancer cells is regulated at least in part, by Sp1. Indole-3-carbinol (I3C) and its acid condensation product, 3,3’-diindolylmethane (DIM) modulate various transcription factors involved in regulating cellular proliferation and apoptosis. The objective of this study was to determine whether reductions in breast cancer cell proliferation caused by I3C and/or DIM occur as a result of reductions in FAS. DIM and, in some cases, I3C reduced FAS expression in three breast cancer cell lines. However, addition of palmitate or oleate to DIM-treated MCF-7 cells did not restore proliferation. DIM-associated reduction in proliferation of MCF-7 cells also results in a reduction of Sp1 expression, and down-regulation of FAS occurs after inhibition of proliferation. Thus, the anti-proliferative effect of I3C and DIM may be due to their effect on down-regulating Sp1, which in turn could modify several Sp1-associated genes, including FAS.