Broccoli Compound May Improve Efficacy of Cancer Prodrug
Broccoli, a source of folic acid.
Sulforaphane, found in broccoli and other cruciferous vegetables such as cauliflower and kale, may increase the susceptibility of a subset of cancer to prodrug treatments while avoiding harm to normal tissues.1
This study involved treating colon cancer cells and intestinal cells from healthy participants with sulforaphane at concentrations similar to what reaches the intestines after eating a meal with broccoli. This was a dose that did not, by itself, act to kill the cells.
Sulforaphane was found to increase the concentration of a number of enzymes in the colon cancer cells, including the enzyme AKR1C3, an aldo-keto reductase. Notably, this effect only occurred in colon cancer cells that had elevated levels of AKR1C3; sulforaphane had no influence on colon cancer cells that initially had a very low concentration of AKR1C3.
AKR1C3 is central to the efficacy of the cancer drug PR-104A, currently in development and clinical testing. PR-104A is administered in its inactive form and is converted to its active form by AKR1C3 inside cancer cells. Sulforaphane, the compound from broccoli, was found to increase the efficacy of PR-104A, such that only one-third of the usual dose of PR-104A was needed to kill the cancer cells.
"Since cancer drugs generally have strong side effects, any approach that reduces the dose of medication while maintaining efficacy is always welcome," said Shana J. Sturla, PhD, of ETH Zurich in Switzerland, and corresponding author of the study.
"What's interesting with sulforaphane is that it occurs naturally in our food and is nontoxic in the concentrations we used," said 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."
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.
1. Erzinger MM, Bovet C, Hecht KM, et al. Sulforaphane preconditioning sensitizes human colon cancer cells towards the bioreductive anticancer prodrug PR-104A. PLoS One. 2016;11(3):e0150219. doi:10.1371/journal.pone.0150219.