Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Licochalcone H Targets EGFR and AKT to Suppress the Growth of Oxaliplatin -Sensitive and -Resistant Colorectal Cancer Cells

  • Seung-On Lee (Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University) ;
  • Mee-Hyun Lee (College of Korean Medicine, Dongshin University) ;
  • Ah-Won Kwak (Biosystem Research Group, Department of Predictive Toxicology, Korea Institute of Toxicology) ;
  • Jin-Young Lee (Department of Biological Sciences, Keimyung University) ;
  • Goo Yoon (Department of Pharmacy, College of Pharmacy, Mokpo National University) ;
  • Sang Hoon Joo (College of Pharmacy, Daegu Catholic University) ;
  • Yung Hyun Choi (Department of Biochemistry, College of Korean Medicine, Dong-Eui University) ;
  • Jin Woo Park (Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University) ;
  • Jung-Hyun Shim (Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University)
  • Received : 2023.09.05
  • Accepted : 2023.09.21
  • Published : 2023.11.01
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Abstract

Treatment of colorectal cancer (CRC) has always been challenged by the development of resistance. We investigated the antiproliferative activity of licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata, in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including pEGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of sub-G1 cells and arrested the cell cycle at the G1 phase. Taken together LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

Keywords

Acknowledgement

This study was funded by the Basic Science Research Program of the National Research Foundation of Korea (NRF) (No. 2019R1A2C1005899) and an NRF grant from the Korean Government (MSIT) (No. 2022R1A5A8033794).

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