Korean Journal of Veterinary Research (대한수의학회지)

The Korean Society of Veterinary Science (대한수의학회)
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Anticancer effect of metformin alone and in combination with 2-deoxy-D-glucose on mouse T cell lymphoma EL4 cells

마우스 T 세포 림프종 EL4 세포에 대한 metformin 단독 및 2-deoxy-D-glucose와 병용의 항암효과

  • Si-Yeon Kim (College of Veterinary Medicine, Jeju National University) ;
  • Hong-Gu Joo (College of Veterinary Medicine, Jeju National University)
  • Received : 2023.07.07
  • Accepted : 2023.09.10
  • Published : 2023.09.30
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Abstract

Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.

Keywords

Acknowledgement

본 연구는 2023학년도 '제주대학교 교원성과지원사업'에 의하여 수행되었으며, 이에 감사드립니다.

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