Arsenic – a promising cancer treatment?

Arsenic has a notorious reputation as a deadly poison, but it could also be used in future cancer treatments according to new research from Stanford University.

Professor of developmental biology Philip Beachy, and Jynho Kim, a postdoctoral scholar in his lab began studying the action of arsenic trioxide in cultured human and mouse cells after observing birth defects caused by arsenic exposure.

The researchers saw that the defects resembled the physical effects of an inactive Hedgehog pathway – a critical cellular signalling cascade. They found that arsenic trioxide blocks the ability of a protein called Gli2 to induce gene transcription in the nucleus, which stops Hedgehog signalling.

“Many pharmaceutical companies are developing anticancer drugs to inhibit the Hedgehog pathway,” said Beachy, “However these compounds target a component of the pathway that can be mutated with patients then becoming resistant to the therapy. Arsenic blocks a different step of the cascade.”

Beachy and Kim discovered that arsenic trioxide disrupts Gli2 production at the end of the pathway, leaving cancer cells little opportunity to mutate and sidestep the drugs inhibitory effect. They studied mice with a type of brain cancer known to be dependent on the Hedgehog pathway and showed that arsenic trioxide slowed or stopped tumour growth.

Current inhibitors like cyclopamine act at the beginning of the pathway by binding to a protein on the surface of the cell called Smoothened and block signals from reaching the cells innards. The researchers combined arsenic trioxide with cyclopamine was even more effective in blocking the signalling pathway in cultured cells.

“Arsenic might be especially effective for treating some types of cancers in combination with other drugs that act at different levels of the Hedgehog pathway, such as the cyclopamine mimics that pharmaceutical companies are developing,” Beachy said.