Artemisia annua L. Polyphenols Enhance the Anticancer Effect of β-Lapachone in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells
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Published:2023-12-15
Issue:24
Volume:24
Page:17505
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Jung Eun Joo1, Kim Hye Jung2ORCID, Shin Sung Chul3, Kim Gon Sup4ORCID, Jung Jin-Myung5, Hong Soon Chan6, Kim Choong Won7, Lee Won Sup1ORCID
Affiliation:
1. Department of Internal Medicine, Institute of Medical Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, 15 Jinju-daero 816 Beon-gil, Jinju 52727, Republic of Korea 2. Department of Pharmacology, Institute of Medical Science, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea 3. Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea 4. Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea 5. Department of Neurosurgery, Institute of Medical Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea 6. Department of Surgery, Institute of Medical Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea 7. Department of Biochemistry, Institute of Medical Science, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea
Abstract
Recent studies suggest that the anticancer activity of β-lapachone (β-Lap) could be improved by different types of bioactive phytochemicals. The aim of this study was to elucidate how the anticancer effect of β-Lap is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in parental HCT116 and oxaliplatin-resistant (OxPt-R) HCT116 colorectal cancer cells. Here, we show that the anticancer effect of β-Lap is more enhanced by pKAL in HCT116-OxPt-R cells than in HCT116 cells via a CCK-8 assay, Western blot, and phase-contrast microscopy analysis of hematoxylin-stained cells. This phenomenon was associated with the suppression of OxPt-R-related upregulated proteins including p53 and β-catenin, the downregulation of cell survival proteins including TERT, CD44, and EGFR, and the upregulation of cleaved HSP90, γ-H2AX, and LC3B-I/II. A bioinformatics analysis of 21 proteins regulated by combined treatment of pKAL and β-Lap in HCT116-OxPt-R cells showed that the enhanced anticancer effect of β-Lap by pKAL was related to the inhibition of negative regulation of apoptotic process and the induction of DNA damage through TERT, CD44, and EGFR-mediated multiple signaling networks. Our results suggest that the combination of pKAL and β-Lap could be used as a new therapy with low toxicity to overcome the OxPt-R that occurred in various OxPt-containing cancer treatments.
Funder
Ministry of Education
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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