β-Lapachone Exerts Anticancer Effects by Downregulating p53, Lys-Acetylated Proteins, TrkA, p38 MAPK, SOD1, Caspase-2, CD44 and NPM in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells
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Published:2023-06-07
Issue:12
Volume:24
Page:9867
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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 Sup4, Jung Jin-Myung5, Hong Soon Chan6, Kim Choong Won7, Lee Won Sup1ORCID
Affiliation:
1. Department of Internal Medicine, Institute of Health Sciences, 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 Health Sciences, 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 Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea 6. Department of Surgery, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea 7. Department of Biochemistry, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea
Abstract
β-lapachone (β-Lap), a topoisomerase inhibitor, is a naturally occurring ortho-naphthoquinone phytochemical and is involved in drug resistance mechanisms. Oxaliplatin (OxPt) is a commonly used chemotherapeutic drug for metastatic colorectal cancer, and OxPt-induced drug resistance remains to be solved to increase chances of successful therapy. To reveal the novel role of β-Lap associated with OxPt resistance, 5 μM OxPt-resistant HCT116 cells (HCT116-OxPt-R) were generated and characterized via hematoxylin staining, a CCK-8 assay and Western blot analysis. HCT116-OxPt-R cells were shown to have OxPt-specific resistance, increased aggresomes, upregulated p53 and downregulated caspase-9 and XIAP. Through signaling explorer antibody array, nucleophosmin (NPM), CD37, Nkx-2.5, SOD1, H2B, calreticulin, p38 MAPK, caspase-2, cadherin-9, MMP23B, ACOT2, Lys-acetylated proteins, COL3A1, TrkA, MPS-1, CD44, ITGA5, claudin-3, parkin and ACTG2 were identified as OxPt-R-related proteins due to a more than two-fold alteration in protein status. Gene ontology analysis suggested that TrkA, Nkx-2.5 and SOD1 were related to certain aggresomes produced in HCT116-OxPt-R cells. Moreover, β-Lap exerted more cytotoxicity and morphological changes in HCT116-OxPt-R cells than in HCT116 cells through the downregulation of p53, Lys-acetylated proteins, TrkA, p38 MAPK, SOD1, caspase-2, CD44 and NPM. Our results indicate that β-Lap could be used as an alternative drug to overcome the upregulated p53-containing OxPt-R caused by various OxPt-containing chemotherapies.
Funder
Ministry of Education
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference51 articles.
1. Beta-lapachone: Natural occurrence, physicochemical properties, biological activities, toxicity and synthesis;Gomes;Phytochemistry,2021 2. A comprehensive review on beta-lapachone: Mechanisms, structural modifications, and therapeutic potentials;Gong;Eur. J. Med. Chem.,2021 3. Pharmacological stimulation of NADH oxidation ameliorates obesity and related phenotypes in mice;Hwang;Diabetes,2009 4. beta-lapachone induces cell cycle arrest and apoptosis in human colon cancer cells;Huang;Mol. Med.,1999 5. Beta-lapachone-mediated apoptosis in human promyelocytic leukemia (HL-60) and human prostate cancer cells: A p53-independent response;Planchon;Cancer Res.,1995
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