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.
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Authors | Seung-On Lee, Mee-Hyun Lee, Ah-Won Kwak, Jin-Young Lee, Goo Yoon, Sang Hoon Joo, Yung Hyun Choi, Jin Woo Park, Jung-Hyun Shim |
Journal | Biomolecules & therapeutics
(Biomol Ther (Seoul))
Vol. 31
Issue 6
Pg. 661-673
(Nov 01 2023)
ISSN: 1976-9148 [Print] Korea (South) |
PMID | 37899744
(Publication Type: Journal Article)
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