J Cancer Prev.  2025 Mar;30(1):24-31. 10.15430/JCP.24.032.

Domperidone Induces Apoptosis through Suppression of STAT3 Signaling in Human Renal Cancer Caki-2 Cells

• Park G
• Baniya MK
• Cha EJ
• Sim SJ
• Choi JS
• Chun KS

• KMID: 2566788
• DOI: http://doi.org/10.15430/JCP.24.032

Abstract

Renal cancer continues to offer a great challenge for its successful therapy today, thus underscoring the need for effective chemotherapeutic agents. In the current study, we explored the anticancer effects of domperidone, a dopamine D2 receptor (DRD2) antagonist, in renal cancer Caki-2 cells. Domperidone induced dose and time-dependent cytotoxic effects in Caki-2 cells, triggering intrinsic apoptosis via the stimulation of the caspase cascade and PARP cleavage. The cytotoxic effect of domperidone was found to be partially DRD2-dependent. Domperidone treatment markedly augmented the production of intracellular reactive oxygen species which induced the cell death of Caki-2 cells. In addition, domperidone suppressed Janus kinase 2 and STAT3 phosphorylation, leading to inhibition of survival and proliferation of these cells. Hence, domperidone can be considered a promising candidate for renal cancer treatment.

Keyword

Domperidone; Apoptosis; STAT3 transcription factor; Reactive oxygen species; Kidney neoplasms