Express-News: San Antonio researchers check synthetic version of capsaicin — the heat in chile peppers — for cancer-killing effects

By Lauren Caruba, San Antonio Express-News

It’s known for giving chile peppers their spice, causing a burning sensation in any tissue it comes in contact with.

But the properties of capsaicin could have a deeper significance. The relationship between pain and capsazepine, a synthetic version of the naturally occurring compound, was what led San Antonio researchers to study whether it could be used to combat oral and other types of cancer.

Researchers at UT Health San Antonio, in collaboration with the University of Texas at San Antonio, have developed a new class of drugs called capsazepine analogs, which bear structural similarities to capsaicin. In preclinical testing on mice, the drugs have shown promise in dramatically reducing the size of tumors.

Cara Gonzales, an associate professor at UT Health San Antonio’s comprehensive dentistry department, starting working with capsazepine several years ago, when she was studying ways to reduce pain from oral cancer.

As part of that work, Gonzales examined how oral tumors activate a certain pain receptor that regulates body temperature — the same receptor that triggers a burning sensation in the mouth after eating jalapeños. Capsazepine was among the compounds that could block that receptor, thus reducing patients’ pain.

As it turns out, it is also effective at targeting and killing cancer cells, Gonzales discovered. The drug has been thoroughly studied in connection with pain reduction and other therapeutic interventions, but its effect on cancer was not previously known.

That finding led her to work with the Center for Innovative Drug Discovery, a partnership between UT Health San Antonio and UTSA that was formed in 2012. Soon after its establishment, Gonzales tapped the center’s chemistry laboratory, housed at UTSA, to produce modifications of capsazepine with a maximized ability to fight cancer.

To date, the lab has produced 47 capsazepine analogs for research spearheaded by Gonzales, said Stanton McHardy, director of the center’s medicinal chemistry lab.

The research team’s work with capsazepine analogs was published in November in the journal Bioorganic and Medicinal Chemistry and in February in the Journal of Oral Pathology and Medicine.

In two sets of experiments on small groups of mice that had been implanted with oral cancer from humans, researchers injected capsazepine analogs directly into the tumors and administered the drugs systemically, or how a patient would normally receive a cancer therapy.

When the analogs were injected, the tumors in the mice shrank by 90 percent. When they were metabolized by the mice every other day over the course of three weeks, some tumors disappeared, while others shrank “to the size of a grain of rice,” Gonzales said.

Researchers also conducted cell culture tests where the analogs were administered in combination with a chemotherapy drug for head and neck cancer. In those tests, the cancerous cells were “completely abolished,” Gonzales said.

Previous experiments on cultures of other types of cancer, including cervical, breast, prostate and lung, also had strong results, she said.

It is not entirely clear why the capsazepine analogs are so effective at eradicating cancer while sparing healthy tissue. But Gonzales said the team’s working theory is that it has something to do with the compound’s effect on tumors’ mitochondria, commonly known as the “powerhouse” of cells.

Cancerous tumors grow more rapidly than healthy cells, making them more reliant on the energy provided by mitochondria and more susceptible to a disruption of that function.

“That’s exactly what we’re trying to figure out: what makes it selective,” Gonzales said. “We think that these drugs can interfere with the mitochondria of the cancer cells, and they’re so dependent on that that it kills them.”

The research remains in its early stages. It could be years before a capsazepine analog is tested in humans, if one makes it to clinical trials at all. However, Gonzales said the work could potentially advance future treatment of oral cancer, for which few drugs have been developed in the past few decades.

McHardy called the work “unique.”

“The molecules are novel, and it’s an approach to the cancer that I don’t think other people are looking at now,” he said.

See the Express-News coverage of this story.

Read more about Dr. Gonzales’ research.



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