|Newly discovered compound make cancer cells more sensitive|
to chemotherapeutic drugs.
Researchers report that a new class of chemical compounds makes cancer cells more sensitive to chemotherapeutic drugs. They have also pinpointed the relevant target enzyme, thus identifying a new target for anti-tumor agents. The research was published in Angewandte Chemie – International Edition.
Researchers have identified a class of chemicals that represent a potential new weapon in the fight against malignant tumors. The compound is itself non-toxic, but it stimulates the killing of rapidly dividing cells by chemotherapeutic drugs. This sensitizing effect means that the latter can be used in lower doses, which makes it less likely that the target cells will become resistant to their lethal effect.
Chemotherapy of malignant tumors is complicated by the fact that, over time, rapidly dividing cancer cells tend to become resistant to the drugs used. The new research has led to the discovery of new class of chemical compounds, referred to as T8, which specifically sensitizes cells to the effect of the anti-cancer drug etoposide, which inhibits the growth of tumor cells by inducing the formation of breaks in the DNA. The scientists have also identified protein disulfide isomerase (PDI) as the target of the new agents. PDI is an enzyme that modifies the spatial conformation, and thus the functional state, of proteins involved in a wide variety of cellular functions.
A major advantage of the new compound is that it is intrinsically non-toxic. Moreover, its functional impact on its target enzyme is reversible. Only when it is administered together with a chemotherapeutic agent do its effects on cellmetabolism manifest.