Diindolylmethane (DIM) Interactions with Cancer Metabolism

Chest
In normal tissue, POOR (300nM) can activate the ATM genetic repair path in answer to diffusion damage in a manner influenced by BRCA1 (one of its targets) without increasing survival of breast tumor cells (MDA-MB-231); there are known alterations in this pathway in some breasts cancers where BRCA1 is reduced while ATM itself is apparently hyperactive, and mouth supplementation of 300mg DARKISH has been noted to increase BRCA1 mRNA levels after 4-6 weeks supplements (measured in white blood cells) in women who a new low activity changement.

A couple of animal studies (using DIM or its progenitor I3C) finding anticancer results on breast cancer cells note that these changes occur alongside increases in 2-hydroxylation of estradiol, which appears to be dose-dependent up to very large oral doses (5, 000ppm in mice or over 10g/kg relative to body weight).

Mechanistically, DIM appears to raise the activity of a genetic repair enzyme which is reduced in some breast cancers which is thought to confer protective effects. The actions on 2-hydroxylation also appear to be relevant as they may confer an antiestrogenic effect
In rats, mouth ingestion of indole-3-carbinol (I3C) for a week prior to induction of mammary cancer via DMBA significantly reduced incidence (70-90%) and multiplicity (91-96%) relative to carcinogen control, also demonstrating efficacy on the primary acting carcinogen N-Nitroso-N-methylurea but to a lesser level (65% reduction in multiplicity).

Spontaneous rather than toxin-induced tumor growth also shows up to be just below halved in one study (lasting 250 days) in rats fed 64-128mg/kg I3C in your editing (estimated intake relative to bodyweight being 4. 8-9. 6g/kg) compared to control, with multiplicity also being somewhat reduced.

 Cervical and Uterine
In rats susceptible to endometrial cancer (Donryu rats) given dietary levels of indole-3-carbinol (I3C; 200-1, 000ppm) and assessed for a prolonged experimental period, rates of spontaneous neoplasms in the uterus after 660 days were significantly higher in controls (38%) rather than the low dose of I3C (25%) with 600-1, 000ppm executing equally (14-16%); this impact was seen alongside increased 2-hydroxylation of estradiol.

Prostatic
DIM has been observed to antagonize the outcomes of dihydrotestosterone (DHT) in prostatic cancer cells (LNCaP and PC-3) by more than 50% at a concentration of 1μM in a manner dependent on the androgen receptor, it appeared to be a direct villain at the receptor with similar affinity as Casodex.

The anticancer effects of DIM at the level of the prostate mobile do not look like totally dependent on this radio though nor are they determined by p53 and can induce cell arrest in a way dependent on inducing p27(Kip1) via Sp1 (10μM), two proteins that tend to have lower activity in androgen-independent prostate tissue. This was downstream p38 proven to occur with DIM in other cancer cells as well.