Image courtesy of PNAS
A class of newly discovered compounds can kill multidrug-resistant lymphoma cells by blocking the cells’ defenses against drugs, according to a study published in Bioorganic & Medicinal Chemistry Letters.
Researchers found this class of molecules—called selenocompounds—could kill multidrug-resistant murine T-lymphoma cells.
In fact, 4 of the compounds triggered apoptotic events in more than 80% of the cells.
“Our research reports a new way to fight multidrug resistance in cancer,” said study author Enrique Domínguez-Álvarez, PhD, of the University of Navarra in Pamplona, Spain.
“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.”
In previous studies, Dr Domínguez-Álvarez and his colleagues discovered 57 new molecules— selenocompounds—that prevented the growth of, and even killed, cancer cells.
While reading up on similar compounds, the researchers found that some could enhance the potency of chemotherapy drugs, so they decided to investigate.
When faced with aggressive treatment, cancer cells can sometimes develop a defense mechanism called an efflux pump—a protein in the cell membrane that can push the drug back out of the cancer cell to protect it. One such protein is called ABCB1.
Dr Domínguez-Álvarez and his colleagues tested the selenocompounds to see if they stopped this mechanism from working and found that the compounds do block the ABCB1 pump, effectively shutting down the defense mechanism.
In fact, 4 of the compounds were stronger inhibitors of the ABCB1 pump than the reference inhibitor the team tested, verapamil (1.7–3.6-fold stronger).
These 4 compounds were also significantly more cytotoxic than verapamil or thioridazine. The compounds triggered apoptotic events in more than 80% of the examined multidrug-resistant mouse T-lymphoma cells.
Dr Domínguez-Álvarez and his colleagues said the next step for this research will be to synthesize similar compounds to determine the most promising derivatives.
Dependent on funding, the team will consider further steps as well, such as testing the compounds in vivo.
