Sulforaphane

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Sulforaphane is readily metabolized and inter-converted into erucin upon ingestion

Given its anticarcinogenic, anti-inflammatory, antioxidant properties, these authors conclude that sulforaphane could be considered as a phytochemical at the forefront of natural medicine.

Sulforaphane was found to be a potent in vitro inducer of the phase II enzymes quinone reductase (QR) and glutathione S-transferase (GST). Sulforaphane also induces phase II enzymes in vivo. In mice treated orally with sulforaphane, QR and GST were increased in many organs, including the liver. It is a potent inducer of the multiorgan protector pathway and hence initiates the cytoplasmic transcription factor NrF2 to migrate into the cell nucleus, where it activates the antioxidant response element, upregulating the production of antioxidant and phase II enzymes.

The induction of phase II enzymes is one of the main mechanisms by which sulforaphane exerts its chemopreventative activity. Orally administered sulforaphane has been shown to be protective against carcinogen-induced cancer at a variety of sites. Taken together these findings suggest that sulforaphane can inhibit the development of cancer during the initiation and post-initiation stages.

The chemopreventative activity of sulforaphane probably involves many mechanisms. These include:

Inhibition of phase I enzymes
Induction of phase II enzymes
Antioxidant functions through increased tissue glutathione levels
Apoptosis-inducing properties
Induction of cell cycle arrest
Anti-inflammatory properties
Inhibition of angiogenesis

A randomized, placebo-controlled trial found that sulforaphane exerted a phase II inducing effect in participants who achieved a good bioavailability (that is, who were able to convert glucoraphanin to sulforaphane in their intestine). Two hundred healthy volunteers from a region in China with a high risk for development of hepatocellular carcinoma were enrolled. Urinary levels of the markers of two environmental carcinogens were assessed. A strong, highly significant inverse association was observed when the marker levels were compared with levels of dithiocarbarnate excretion (a measure of the metabolism of glucoraphanin). Oral administration of a broccoli sprout homogenate over 3 days induced mucosal phase II enzyme expression in the upper airway of human volunteers. (Bone & Mills, pg 32)

Due to its high lipophilicity and its low molecular weight, the SF is rapidly

absorbed by the intestinal epithelium. It is conjugated to glutathione (GSH) by the enzyme glutathione S-transferase (GST) and it follows the mercapturic pathway with the excretion of N-acetyl cysteine in the urine. As a result, the SF metabolism and excretion depend on the GST activity and consequently

they are influenced by the polymorphism of GST’s subunits, especially GST-M1 and GST-T1

The likelihood of null genotype of these isoforms is relatively high in Caucasian and Asian population and it leads to a different SF biodistribution with an altered protective and anti-cancer activity.

Broccoli sprout beverage is safe for thyroid hormonal and autoimmune status.

Broccoli sprout-derived products are promising agents for the prevention of oxidative stress-related diseases, but some have long been suspected of thyroidal toxicity. Recent findings also raise the possibility that long-term exposure to sulforaphane, or to other natural substances or drugs that modulate the activity of the transcription factor Nrf2 (NFE2-related factor 2) may lead to thyroid dysfunction or thyroid autoimmune disease, questioning the safety of trials with sulforaphane-containing products. Previous studies addressing possible effects of sulforaphane-related compounds from natural product extracts on the thyroid were quite short and/or inconsistent. To investigate whether long-term exposure to a beverage enriched with sulforaphane and its precursor glucoraphanin may affect thyroid function, we analyzed biochemical measures of thyroid function and thyroid autoimmunity in 45 female participants in a randomized clinical trial at baseline and after 84 days of beverage administration. Serum levels of thyroid-stimulating hormone, free thyroxine and thyroglobulin were not affected by the treatment, and neither was the thyroid autoimmunity status of participants. These results provide evidence in favor of the safety of chemoprevention strategies that target the activation of Nrf2 to protect against environmental exposures and other oxidative stress-related pathologies.

Role in Colon Cancer

Sulforaphane appears to play a complex role in colon cancer, with both potential protective and promotional effects:

Chemopreventive effects:

Sulforaphane has shown chemoprotective effects against colon cancer, likely by upregulating Nrf2-dependent antioxidant enzymes in normal colonic epithelial cells 1.
It can induce apoptosis of colonic tumor cells through inhibition of histone deacetylase (HDAC) activity 1.

Effects on cell proliferation:

At low doses, sulforaphane can promote cell proliferation in HCT116 human colon cancer cells expressing normal p53 2.
Higher doses (≥10 μM) caused cell death, with a more pronounced effect in p53-deficient cells 2.

Apoptosis induction:

Sulforaphane can induce apoptosis in colon cancer cells through various mechanisms, including:
Translocation of phosphatidylserine
Chromatin condensation
Increased expression of pro-apoptotic protein Bax
Release of cytochrome c from mitochondria to cytosol
Proteolytic cleavage of poly(ADP-ribose) polymerase 3

Cell cycle effects:

Sulforaphane can induce cell cycle arrest in a dose-dependent manner, correlated with increased expression of cyclins A and B1 3.

Gene expression changes:

Next-generation sequencing studies show that sulforaphane affects multiple signaling pathways in colon cancer cells, including p53, MAPK, FOXO, and Wnt signaling pathways 4.

In vivo effects:

Low-dose sulforaphane promoted tumor growth in p53-wild-type HCT116 xenografts in mice, while having little effect at medium or high doses 2.

Potential risks:

Some research suggests that sulforaphane intake could potentially be harmful to colorectal cancer patients carrying the wild-type p53 gene, due to its Nrf2-activating capabilities 2.