Transient induction of cytochromes P450 1A1 and 1B1 in MCF-7 human breast cancer cells by indirubin

7-Bromoindirubin-3′-oxime induces caspase-independent cell death

“…Antitumor activity of 7-bromoindirubin-3 0 -oxime J Ribas et al (Adachi et al, 2001;Spink et al, 2003;Knockaert et al, 2004;Sugihara et al, 2004). 7-Bromoindirubin-3 0 -oxime clearly activates AhR as observed in an in vitro luciferase reporter system (unpublished), and confirmed by the AhR-dependent expression of p27…”

NF‐κB and epithelial to mesenchymal transition of cancer

“…Historically, the AhR has been studied for its responsiveness to a variety of environmental chemicals (e.g., polycyclic aromatic hydrocarbons, PCBs, and dioxins) and its ability to transactivate genes encoding phase I cytochrome P-450 enzymes that metabolize endogenous substrates (e.g., 17b-estradiol) and some environmental chemicals into mutagenic intermediates [Safe and Krishnan, 1995;Spink et al, 2003]. However, more recent studies have indicated roles for the AhR, even in the absence of environmental ligands, in the transcriptional regulation of genes critical for growth [Ma and Whitlock, 1996;Elizondo et al, 2000;Tohkin et al, 2000;Abdelrahim et al, 2003;Patel et al, 2006], apoptosis Patel et al, 2006;Wu et al, 2007], and in EMT and tumor progression [Mulero-Navarro et al, 2005].…”

A systems approach to traditional oriental medicine

“…Mapping metabolites structurally similar to TOM compounds should be useful in narrowing down the candidate pathways and/or reactions for elucidating the mechanisms of action of the TOM-derived synergistic effects (see below). For instance, metabolites (e.g., carbamazepine, 2-hydroxycarbamazepine and 3-hydroxycarbamazepine) similar to indirubin found in Realgar-Indigo naturalis formula appeared to be involved in drug metabolism (Supplementary Table 2), and, in fact, indirubin has been known to induce drug metabolism by activating cytochromes 23 . Interestingly, in the case of danshensu, whose similar metabolites are largely associated with tyrosine metabolism (e.g., 3-(4-hydroxyphenyl)lactate, 3,4-dihydroxy-l-phenylalanine, 2-carboxy-2,3-dihydro-5,6-dihydroxyindole, 3-(4-hydroxyphenyl)pyruvate, and l-tyrosine; Supplementary Table 2), it was shown to inhibit tyrosine phosphorylation, thereby contributing to maintaining cell-cell adhesion 24 .…”