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Domperidone Induces Apoptosis through Suppression of STAT3 Signaling in Human Renal Cancer Caki-2 Cells
Geumi Park1,2, Manoj Kumar Baniya1, Eun-Jeong Cha1
1College of Pharmacy, Keimyung University, Daegu, Korea.
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.
Insights
Domperidone, a dopamine D2 receptor antagonist, shows promise for renal cancer treatment. It effectively kills renal cancer cells by triggering apoptosis and reducing cell survival pathways.
Area of Science:
- Oncology
- Pharmacology
Background:
- Renal cancer therapy remains challenging, necessitating novel chemotherapeutic agents.
- Domperidone, a known dopamine D2 receptor (DRD2) antagonist, has potential anticancer properties.
Purpose of the Study:
- To investigate the anticancer effects of domperidone on renal cancer Caki-2 cells.
- To elucidate the mechanisms underlying domperidone's cytotoxic activity in renal cancer.
Main Methods:
- Utilized Caki-2 renal cancer cells for in vitro studies.
- Assessed domperidone's dose- and time-dependent cytotoxic effects.
- Analyzed apoptosis induction, reactive oxygen species (ROS) production, and signaling pathways (JAK2/STAT3).
Main Results:
- Domperidone exhibited dose- and time-dependent cytotoxicity in Caki-2 cells.
- Apoptosis was triggered via caspase cascade activation and PARP cleavage, partially dependent on DRD2.
- Domperidone increased intracellular ROS, leading to cell death.
- Inhibited Janus kinase 2 (JAK2) and STAT3 phosphorylation, suppressing cell survival and proliferation.
Conclusions:
- Domperidone demonstrates significant anticancer effects against renal cancer cells.
- The drug induces cell death through apoptosis and ROS generation, involving DRD2 and JAK2/STAT3 pathways.
- Domperidone presents a promising therapeutic candidate for renal cancer treatment.
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