Vegetarians are wimps: Science now tells us why

Oh, it started innocently enough. Population studies had shown that men who ate lots of cruciferous vegetables (collard greens, cabbage, brussels sprouts, broccoli, cauliflower, bok choy etc. etc.) had less prostate cancer. Some folks in Oregon decided to find out why [ Proc. Natl. Acad. Sci. vol. 106 pp. 16663 – 16668 ’09 ]. One of the compounds found in all these veggies is sulforaphane. There are all sorts of places to be found on the web that will sell it to you for your health. Sulforaphane is said to fight cancer, improve diabetes and kill bacteria (if you believe Wikipedia). Hosanna.

Prostate cancer is made worse by male hormones (androgens). They produce their effects in cells by binding to a protein (the androgen receptor) which then goes into the nucleus of the cell and turns on the genes which make males male. If there’s no androgen around the receptor just sits there outside the nucleus (e.g. in the cytoplasm), doing nothing. Some forms of prostate cancer have mutations in the receptor which turn it on whether androgen is present or not. This makes the cancer even worse. So one of the mainstays of prostate cancer therapy is lowering androgen levels by a variety of means, none of them pleasant — such as castration and various pills.

The Oregon work shows that sulforaphane decreases the amount of androgen receptor around resulting in less androgenic effects, and presumably less prostate cancer in the long run. How this is thought to occur is pretty interesting, highly technical and is to be found in subsequent paragraphs. It also explains why vegetarians are such wimps.

The androgen receptor sits in the cytoplasm bound to a protein called HSP90 (heat shock protein of 90 kiloDaltons). This protects the androgen receptor from being destroyed. Sulforaphane is a fairly simple molecule — a straight 4 carbon chain with a methyl sulfoxide group at one end and an isothiocyanate (-N=C=S ) group at the other. It should be pretty lipid soluble, meaning it can go everywhere in the body without much trouble. The authors showed that sulforaphane inhibits an enzyme called histone deacetylase 2 (HDAC2). This results in more acetylation of HSP90 on lysine, inhibiting the association of HSP90 with the androgen receptor, leading to increased destruction of the receptor and less androgenic effects in the cell.

The active site of one histone deacetylase that we know about is a tubular pocket containing a zinc binding site and two aspartic acid histidine charge relay systems. My guess is that the business end of sulforaphane is the isothiocyanate, which could react by nucleophilic attack of either the histidine nitrogen or the aspartic acid oxygen on the carbon of the -N=C=S group. Perhaps one of readers knows how it works.

Histone deacetylase inhibitors are presently very ‘hot’ and one of them, SAHA was approved by the FDA for the treatment of T cell cutaneous lymphoma in 2007, and many others are under active investigation. It’s important to remember that although this class of enzymes was discovered by their ability to remove acetyl groups from histones, they also remove acetyl groups from proteins which are not histones (e.g. HSP90).

So veggies are a two-edged sword.

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Comments

  • Todd  On November 29, 2011 at 7:49 am

    Interesting post, but it does lead to one question. As you may know, African-Americans traditionally eat collard greens as a regular part of their vegetable intake. However, African-Americans also have higher prostate cancer rates than average. Any good studies that square these two facts?

  • luysii  On November 29, 2011 at 11:22 am

    Good point. I know of no studies on your point, but the paper is relatively new (’09).

    However, the genetic background of African Americans is much closer to African blacks than to the US population as a whole. The admixture of European gene variants in the US black population is thought to be around 20%. This might explain the difference. We are just coming to appreciate the importance of genetic background on disease expression. See https://luysii.wordpress.com/2011/07/17/weve-found-the-mutation-causing-your-disease-not-so-fast-says-this-paper/

    Go Rutgers ! My whole family went there.

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