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.

PubMed

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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