Antitumor activity of silver (Ag) complexes in colorectal cancer cells by oxidative stress and apoptosis induction.

AIMS: Metal-based drugs, such as the platinum-derived compounds cisplatin and oxaliplatin, are routinely used in cancer therapy. Currently, among these, only oxaliplatin has demonstrated significant efficacy in colorectal cancer (CRC). This urges the necessity of developing more effective anticancer agents.

MATERIALS AND

METHODS

Two bis(phosphine)silver(I) complexes with a general formula of (Ph3P)2AgCl{ROC(=S)N(H)Ph, with R = Me (Ag1) and Et (Ag2) were prepared to evaluate their anticancer effects and underlying mechanisms of action in CRC cells.

RESULTS AND

CONCLUSIONS

The precursor ((Ph3P)2AgCl; Ag) and its complexes bearing a thiocarbamide moiety effectively inhibited the proliferation of HCT116 and HT-29 CRC cells. Notably, Ag1 and Ag2 demonstrated potent activity in disintegrating 3D spheroids, surpassing the efficacy of both the Ag precursor and cisplatin. Mechanistic investigations revealed that Ag and Ag1 induced the production of reactive oxygen species (ROS) and superoxide in CRC cells, while all Ag complexes including the precursor triggered cell apoptosis. The collective findings indicate that the synthesized Ag complexes potently kill CRC cells through oxidative stress induction and programmed cell death.