Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Doxorubicin Attenuates Free Fatty Acid-Induced Lipid Accumulation via Stimulation of p53 in HepG2 Cells

  • Chawon Yun (Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University) ;
  • Sou Hyun Kim (Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University) ;
  • Doyoung Kwon (College of Pharmacy, Jeju Research Institute of Pharmaceutical Sciences, Jeju National University) ;
  • Mi Ran Byun (College of Pharmacy, Daegu Catholic University) ;
  • Ki Wung Chung (Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University) ;
  • Jaewon Lee (Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University) ;
  • Young-Suk Jung (Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University)
  • Received : 2023.11.09
  • Accepted : 2023.11.14
  • Published : 2024.01.01
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Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver, and there is a global increase in its incidence owing to changes in lifestyle and diet. Recent findings suggest that p53 is involved in the development of non-alcoholic fatty liver disease; however, the association between p53 expression and the disease remains unclear. Doxorubicin, an anticancer agent, increases the expression of p53. Therefore, this study aimed to investigate the role of doxorubicin-induced p53 upregulation in free fatty acid (FFA)-induced intracellular lipid accumulation. HepG2 cells were pretreated with 0.5 ㎍/mL of doxorubicin for 12 h, followed by treatment with FFA (0.5 mM) for 24 h to induce steatosis. Doxorubicin pretreatment upregulated p53 expression and downregulated the expression of endoplasmic reticulum stress- and lipid synthesis-associated genes in the FFA -treated HepG2 cells. Additionally, doxorubicin treatment upregulated the expression of AMP-activated protein kinase, a key modulator of lipid metabolism. Notably, siRNA-targeted p53 knockdown reversed the effects of doxorubicin in HepG2 cells. Moreover, doxorubicin treatment suppressed FFA -induced lipid accumulation in HepG2 spheroids. Conclusively, these results suggest that doxorubicin possesses potential application for the regulation of lipid metabolism by enhance the expression of p53 an in vitro NAFLD model.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (NRF-2019R1I1A3A01058584) and the Commercializations Promotion Agency for R&D Outcomes (COMPA) grant funded by the Korea government (MSIT) (No. 2021N400).

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