Many cancer deaths occur because cancer cells develop resistance to chemotherapy drugs, prompting a field of research bent on overcoming this treatment barrier. An important step forward took place recently when researchers showed a newly discovered class of molecules can kill mouse cancer cells that have become multi-drug resistant.
The team, including members from the University of Navarra in Pamplona, Spain, and Jagiellonian University Medical College in Kraków, Poland, describes their work so far with the new class of drugs – called selenocompounds – in the journal Bioorganic & Medicinal Chemistry Letters.
Lead author Dr. Enrique Domínguez-Alvarez, from both the University of Navarra and Jagiellonian University, says:
“Our research reports a new way to fight multi-drug resistance in cancer. We are realistic and we know that much more research needs to be done, but we are excited about these promising results that open new and unexplored possibilities.”
The new study arises from previous work that identified 57 compounds with anti-cancer properties, among which the team believed there were some that might boost the power of chemotherapy drugs.
The study focuses on a common defense mechanism called the “efflux pump” that develops in cancer cells exposed to chemotherapy.
Situated inside cell membranes, efflux pumps are proteins that push toxic compounds like chemotherapy drugs out of the cell. One such protein is called ABCB1.
The team wanted to see if the selenocompounds discovered in previous work could block the ABCB1 efflux pump.
After running various test-tube experiments with multi-drug resistant (MDR) mouse T-lymphoma cells, the researchers showed the compounds blocked the efflux pumps, with some working four times more effectively than others.
They also found the compounds can trigger apoptosis – cell suicide – in cancer cells.
The most active of the selenocompounds they tested killed about 80 percent of the mouse cancer cells.
The researchers conclude that four of the 11 selenocompounds they tested “demonstrated high potency to inhibit cancer MDR efflux pump ABCB1 with simultaneous cytotoxic- and strong pro-apoptotic activities in the mouse T-lymphoma cells.”
They acknowledge these results are just the start of the long process of developing a new class of pharmaceutical drugs.
The next step will be to make and screen similar compounds to select the ones with most potential for testing in live animals.
“I hope that in the future our work will serve as the basis to develop new drugs against cancer that reach the patients who need them.”
Dr. Enrique Domínguez-Alvarez