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Differential effects of broccoli‐derived phytochemicals indole‐3‐carbinol and its dimer 3, 3’‐diindolylmethane on liver X receptor‐responsive genes in human prostate cancer cells

This study examined the effects of indole‐3‐carbinol (I3C) and 3, 3’‐diindolylmethane (DIM) on liver X receptor (LXR)‐dependent pathways. DIM, but not I3C, induced transcription of ABCG1 and ABCA1 mRNA, two LXR‐responsive ATP‐binding cassette transporters involved in cholesterol efflux, in the androgen responsive LNCaP cells, but not the androgen non‐responsive PC3 cells. Exposure of LNCaP cells to 5 microM DIM for 48 hrs led to a 5‐fold increase in ABCG1 and ABCA1 mRNA levels. Knockdown of LXR alpha and beta isoforms using siRNA abrogated the ability of DIM to induce ABCG1 but not ABCA1 mRNA. Furthermore, knockdown of androgen receptor (AR) expression in LNCaP cells with AR siRNA blocked DIM induction of ABCA1 and ABCG1 mRNAs. The results suggest that DIM modulates cholesterol metabolism through both androgen‐mediated and LXR‐dependent pathways in prostate cancer cells. Furthermore, these effects are unique to DIM but not I3C suggesting that these two dietary components exert cancer preventive effects through different mechanisms.