A New Class of Gold(I) NHC Complexes with Proapoptotic and Resensitizing Properties towards Multidrug Resistant Leukemia Cells Overexpressing BCL‑2

From previous studies,
it is evident that metal–organic
gold(I) complexes have antiproliferative activities. The aim of this
study is not only to find new anticancer agents but also to overcome
existing cytostatic resistance in cancer cells. The synthesis and
medicinal evaluation of two cationic 1,3-disubstituted gold(I) bis-tetrazolylidene
complexes 1 and 2 are reported. To determine
apoptosis-inducing properties of the complexes, DNA fragmentation
was measured using propidium iodide staining followed by flow cytometry.
Gold(I) complex 1 targets explicitly malignant cells,
effectively inhibiting their growth and selectively inducing apoptosis
without signs of necrosis. Even in cells resistant to common treatments
such as doxorubicin, it overcomes multidrug resistance and sensitizes
existing drug-resistant cells to common cytostatic drugs. It is assumed
that gold(I) complex 1 involves the mitochondrial pathway
in apoptosis and targets members of the BCL-2 family, enhancing its
potential as a therapeutic agent in cancer treatment.