Shiga toxin research at The University of Texas at Austin College of Pharmacy illustrates the benefits of repurposing existing treatments.
By Emily Jacobs
Although many cases of foodborne illness last a few days with no long-term effects, a small percentage can cause serious and even fatal complications. Shiga toxin-producing Escherichia coli (STEC) is responsible for many foodborne illnesses in the United States and other developed countries. Of those people diagnosed with STEC, up to 10 percent can develop life-threatening hemolytic uremic syndrome, a type of kidney failure.
Infections involving Shiga toxin-producing bacteria cause more than 1 million deaths around the world annually, with no current effective treatment. Complicating the issue is the fact that some antibiotics trigger STEC to release more toxin. However, new research suggests that the breast cancer drug tamoxifen may block Shiga toxins from invading human cells and causing disease.
Dr. Somshuvra Mukhopadhyay, assistant professor of pharmacology and toxicology at The University of Texas at Austin College of Pharmacy, has been leading research to better understand how Shiga toxins enter human cells. Research had already indicated that the toxin could be prevented from invading and destroying cells. The surprise for Mukhopadhyay’s team was tamoxifen’s efficacy at doing so.
Tamoxifen works against breast cancer by hindering the effects of estrogen and preventing cancerous cells from growing and replicating abnormally in the breast. Its actions on Shiga toxin, however, are entirely independent of anything related to estrogen. Instead, tamoxifen appears to work against Shiga toxin by changing the acidity of parts of the cell. “It's a totally different chemical activity,” said Mukhopadhyay. “It seems like tamoxifen is acting essentially as a base, [making] certain parts of the cells become more alkaline. So it's a very unexpected mechanism of action.”
It’s a totally different chemical activity. It seems like tamoxifen is acting essentially as a base, [making] certain parts of the cells become more alkaline. So it’s a very unexpected mechanism of action.