Novel compounds could be less toxic

A novel class of compounds developed by a University of Saskatchewan (U of S)-led research team could yield more effective and less toxic chemotherapy drugs to treat cancer. Team leader Jonathan Dimmock, a medicinal chemistry researcher in the U of S College of Pharmacy and Nutrition, explained their compounds work by interacting with thiols, naturally occurring chemicals that perform several roles in cells.

onathan Dimmock and Umashankar Das and their team have developed anti-cancer...
onathan Dimmock and Umashankar Das and their team have developed anti-cancer compounds that work by interacting with thiols, naturally occurring chemicals that perform several roles in cells. Their approach offers advantages over existing chemotherapy drugs.
Source: Michael Robin

The approach offers advantages over existing chemotherapy drugs which target nucleic acids found in DNA. “Many of the compounds or drugs on the market are those that interfere with nucleic acids,” Dimmock said. “These types of compounds can be very toxic and they can also cause problems of their own, like actually inducing cancer.”

Thiols offer another approach. Among their many roles are defending cells against oxidization and modulating apoptosis—the process in which worn-out cells die. One of the hallmarks of cancer cells is they don’t experience apoptosis and keep dividing out of control.

Umashankar Das, a research scientist in the Department of Chemical and Biological Engineering and long-time collaborator of Dimmock, explained that cancer cells produce an excess of thiols, such as one called glutathione. Knocking down levels of these thiols reduces cancer cells’ ability to resist drugs. “In cancer cells, glutathione expression is very high, which creates a defense mechanism,” Das said. “Any anti-cancer compound that enters the cell cannot sustain its effect.”

To address this, the team developed a two-stage attack, first knocking down thiol levels to make the cancer cells vulnerable, then hitting them again. “Over the years, we’ve developed the theory of ‘sequential cytotoxicity,’ which simply means you give an initial attack on the cancer cell and then you give a second chemical attack,” Dimmock said. “The cancer cells may be more vulnerable to the second attack than normal cells.”

Designing molecules that selectively target thiols produced by cancer cells that cause drug resistance is the focus of many years’ work by Dimmock, Das and their collaborators. In their latest study, they tested compounds against cells from nine different types of human cancer, including common types affecting blood, colon, breast, prostate, ovaries, kidneys, and lungs.

Das explained that since the compounds they’ve developed make cancer cells more sensitive to attack, they also remove resistance to standard chemotherapy drugs—a serious problem in current therapies. “Many of our compounds are what we call multi-drug resistance revertants, so we’re actually creating a much more sensitive cancer cell through this process,” he said.

Source: University of Saskatchewan


Read all latest stories

Related articles


Article •

Epigenetic drugs

‘All human body cells contain the same DNA, but every type of cell – for example a muscle cell compared to that of a nerve – has a different gene expression pattern’, said Dr Sonja Stadler,…


News • Open source

Machine Learning tool could help choose cancer drugs

The selection of a first-line chemotherapy drug to treat many types of cancer is often a clear-cut decision governed by standard-of-care protocols, but what drug should be used next if the first one…


News • Reinforced learning

AI masters tightrope walk of cancer treatment dosage

Using a new approach called 'reinforced learning', researchers have taught an artificial intelligence (AI) to responsibly choose the right amount of chemo- and radiotherapy for glioblastoma patients.…

Related products

Subscribe to Newsletter