PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Inhibition of EGFR and AKT Activity by Licochalcone H Inhibits Proliferation and Induces Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells
Version 1
: Received: 8 August 2023 / Approved: 8 August 2023 / Online: 9 August 2023 (03:01:44 CEST)
How to cite:
Lee, S.-O.; Lee, M.-H.; Kwak, A.-W.; Lee, J.-Y.; Yoon, G.; Joo, S. H.; Choi, Y. H.; Park, J. W.; Shim, J.-H. Inhibition of EGFR and AKT Activity by Licochalcone H Inhibits Proliferation and Induces Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells. Preprints2023, 2023080641. https://doi.org/10.20944/preprints202308.0641.v1
Lee, S.-O.; Lee, M.-H.; Kwak, A.-W.; Lee, J.-Y.; Yoon, G.; Joo, S. H.; Choi, Y. H.; Park, J. W.; Shim, J.-H. Inhibition of EGFR and AKT Activity by Licochalcone H Inhibits Proliferation and Induces Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells. Preprints 2023, 2023080641. https://doi.org/10.20944/preprints202308.0641.v1
Lee, S.-O.; Lee, M.-H.; Kwak, A.-W.; Lee, J.-Y.; Yoon, G.; Joo, S. H.; Choi, Y. H.; Park, J. W.; Shim, J.-H. Inhibition of EGFR and AKT Activity by Licochalcone H Inhibits Proliferation and Induces Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells. Preprints2023, 2023080641. https://doi.org/10.20944/preprints202308.0641.v1
APA Style
Lee, S. O., Lee, M. H., Kwak, A. W., Lee, J. Y., Yoon, G., Joo, S. H., Choi, Y. H., Park, J. W., & Shim, J. H. (2023). Inhibition of EGFR and AKT Activity by Licochalcone H Inhibits Proliferation and Induces Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells. Preprints. https://doi.org/10.20944/preprints202308.0641.v1
Chicago/Turabian Style
Lee, S., Jin Woo Park and Jung-Hyun Shim. 2023 "Inhibition of EGFR and AKT Activity by Licochalcone H Inhibits Proliferation and Induces Apoptosis in Oxaliplatin-Sensitive and -Resistant Colorectal Cancer Cells" Preprints. https://doi.org/10.20944/preprints202308.0641.v1
Abstract
Licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata. CRC treatment has always been challenged by the development of resistance. We investigated the antiproliferative activity of LCH 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 phospho (p)-EGFR 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, as verified by N-acetyl-L-cysteine (NAC) treatment, and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP and increased. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of subG1 cells and arrested the cell cycle at the G1 phase. 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
licochalcone H (LCH); oxaliplatin; colorectal cancer; EGFR; AKT; apoptosis
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.