Researchers at RIKEN and Institute of Science Tokyo used carbon monoxide to produce a potential anticancer compound inside cultured cells, but the system showed only modest selectivity over normal fibroblasts.
The findings appeared Sept. 17 in Nature Communications. The approach uses carbon monoxide (CO) associated with cancer-cell metabolism as an ingredient for making a compound where the cells are grown. The experiments did not test treatment in animals or people.
The system, called APC-17, places a palladium catalyst in a pocket of human serum albumin. A coumarin anchor helps guide the catalyst into that pocket, while the albumin protects it from glutathione, a cellular antioxidant that can deactivate the catalyst.
A separate test used APC-9, a probe for detecting CO activity in cells. After 48 hours, researchers measured 136 picomoles of a CO-derived compound per million A549 lung cancer cells, compared with 15 picomoles per million TIG3 fibroblasts. APC-9 was used for detection; APC-17 was the system used to make the drug candidate.
In HepG2 liver cancer cells, APC-17 produced compound 14, a phenanthridinone derivative. The paper estimated the compound’s concentration inside the cells at about 36.4 nanomolar. In a 96-hour cell-viability test, the concentration of APC-17 associated with reducing cell viability by half was 13.99 micromolar in HepG2 cells and 37.54 micromolar in TIG3 fibroblasts. The researchers described the difference as modest.
A separate 12-day assay found that APC-17 reduced colony formation in MCF7 breast cancer cells, with significant inhibition reported at 5 micromolar. In another test, researchers found no compound 10 after incubating the detection probe APC-9 in freshly collected mouse blood for four hours at 37°C. That was an experiment outside a living animal, not a treatment test.
RIKEN said the team had previously explored local compound synthesis in cancer cells using acrolein. The CO study extends that research approach to another molecule, but the researchers identified testing in living systems as future work.
