Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin

  • Seung-On Lee (Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University) ;
  • Sang Hoon Joo (College of Pharmacy, Daegu Catholic University) ;
  • Jin-Young Lee (Department of Biological Sciences, Keimyung University) ;
  • Ah-Won Kwak (Biosystem Research Group, Department of Predictive Toxicology, Korea Institute of Toxicology) ;
  • Ki-Taek Kim (Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University) ;
  • Seung-Sik Cho (Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University) ;
  • Goo Yoon (Department of Pharmacy, College of Pharmacy, Mokpo National 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 : 2023.09.19
  • Accepted : 2023.10.19
  • Published : 2024.01.01
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Abstract

Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

Keywords

Acknowledgement

This study was funded by the Basic Science Research Program of the National Research Foundation of Korea (NRF) (No. 2019R1A2C1005899, 2021R1I1A3058531), and an NRF grant from the Korean Government (MSIT) (No. 2022R1A5A8033794).

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