Could bugs beat broccoli in cancer prevention?

Generations of parents (including this writer) have berated their offspring with the message that green stuff, while looking and tasting yucky, is really, really good for you. And, for all sorts of reasons, including a reduction in lifetime cancer risk, it’s a message worth heeding.

Green is good...

Many fruits and vegetables are rich in metabolites which act directly or indirectly on pre-cancerous or cancer cells to constrain or reverse tumour formation, albeit with limited effect. Daily consumption of a large quantity of fruits and vegetables is required to get even close to preventative metabolite levels, something that does not sit conveniently with most modern lifestyles.

In a neat piece of lateral thinking, a cross-disciplinary research group at the National University of Singapore has engineered a strain of one of the commonest gut bacteria, Escherichia coli, to latch onto colorectal cancer (CRC) cells and express an enzyme that converts an abundant dietary metabolite into a potent cancer inhibitor.

The metabolite of interest, glucosinolate, is found in cruciferous vegetables (brassicas to us Brits), including broccoli, the unfairly maligned Brussels sprout, cauliflower and rocket. Broccoli and its ilk are rich in glucosinolate, a precursor of sulforaphane, a compound known to inhibit cancer in a variety of ways. Sulforaphane production is catalysed by  myrosinase, a plant enzyme that's largely lost during cooking. Gut bacteria can  break down glucosinolate, although not with sufficient efficiency to  maintain useful sulforaphane levels.

The Singapore group was able to demonstrate that, in the test tube, an engineered E.coli strain, designated EcN, inhibited growth of CRC cells, but not cells from breast or stomach cancers or smooth muscle cells.

When tested in a mouse model of CRC, EcN was found to bind to tumour cells in the gut and substantially increase the plasma concentration of metabolites akin to glucosinolate. Tumour burden was reduced by 75%. One unwanted effect was an increase in bleeding in the gut compared with untreated mice, although this may have been related to the mouse cancer model, and not a direct consequence of tumour cell binding.

While raising more questions than answers, this research does hint at the future prospect of being able to boost the limited anti-cancer effect of diet through supplementation by engineered probiotics. Caution is warranted: our understanding of interactions within the gut microbiome is in its infancy and introduction of an engineered arriviste could have subtle and unpredictable consequences.  And, as with other dietary approaches to cancer prevention, generating robust efficacy and safety data presents a significant challenge.

Photo credit:  khumthong at FreeDigitalphotos.net

Engineered commensal microbes for diet- mediatedcolorectal-cancer chemoprevention. Ho, CL et al.  Nature Biomedical Engineering, 2: January 2018; 27–37.

Broccoli-derived sulforaphane and chemoprevention of prostate cancer: From bench to bedside. Amjad,AI et al. Curr Pharmacol Rep. 2015 Nov 1; 1(6): 382–390. http://tinyurl.com/ybvo37sv.