Stuff in broccoli helps drug kill colon cancer

"Since cancer drugs generally have strong side effects, any approach that reduces the dose of medication while maintaining efficacy is always welcome," says Shana Sturla. (Credit: whologwhy/Flickr)

Even small amounts of an ingredient found in broccoli can make a cancer drug work better, new research shows.

Colon cancer cells were more likely to die when they were pretreated with sulforaphane, an ingredient found in cruciferous vegetables, and then treated with a cancer drug currently in development.

The concentration used was equivalent to eating a typical serving of broccoli, and, importantly, at a dose that did not itself act in killing the cells.

This is one of only a few examples of a food ingredient that, in moderate amounts, has a positive influence on the efficacy of a cancer drug.

The researchers from ETH Zurich and the University of Zurich discovered that sulforaphane increases the concentration of a number of enzymes in the colon cancer cells, including those of an enzyme with the abbreviation AKR1C3. Interestingly, sulforaphane does not have this effect in all cases: In colon cancer cells that already exhibit a significantly elevated concentration of AKR1C3 as a result of the cancer, the broccoli substance caused a further increase in the concentration of the enzyme.

But sulforaphane had no influence in colon cancer cells with an initially very low concentration of AKR1C3. The same was found with intestinal cells unaffected by cancer.

Less drug, fewer side effects?

The enzyme AKR1C3 is a biochemical actor in several metabolic pathways in the human body. It is also central in the efficacy of a cancer drug that is currently still in development and clinical testing. This drug, called PR-104A, is administered in an inactive form and is converted into its active form inside the cancer cells by the AKR1C3 present there.

The researchers used cell culture to investigate whether the broccoli ingredient increased the efficacy of PR-104A. When the scientists pre-treated the colon cancer cells with sulforaphane, less than a third of the usual dose of PR-104A was enough to kill the cancer cells.

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“Since cancer drugs generally have strong side effects, any approach that reduces the dose of medication while maintaining efficacy is always welcome,” says Shana Sturla, a professor in health sciences and technology at ETH Zurich.

“What’s interesting with sulforaphane is that it occurs naturally in our food and is nontoxic in the concentrations we used,” says Sturla. “In addition, the sulforaphane-enhancing effect was seen only in cancer cells and not cells from healthy tissue, which would be very important for avoiding unwanted side-effects from the combination”.

Future studies

Based on these results in cell cultures, the scientists aim to conduct biomarker-based clinical studies with cancer patients to investigate whether sulforaphane positively supports a treatment with PR-104A.

The researchers also want to find further food ingredients that positively influence the efficacy of medication, even in small amounts, as well as accompanying biomarkers that can help track personalized responses.

“We assume that there are other such combinations out there,” says Sturla.

The Swiss National Science Foundation supported the work, which was published in the journal PLOS ONE.

Source: ETH Zurich