دورية أكاديمية
Suppression of DYRK1A/B Drives Endoplasmic Reticulum Stress-mediated Autophagic Cell Death Through Metabolic Reprogramming in Colorectal Cancer Cells
| العنوان: | Suppression of DYRK1A/B Drives Endoplasmic Reticulum Stress-mediated Autophagic Cell Death Through Metabolic Reprogramming in Colorectal Cancer Cells |
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| المساهمون: | Jieon Hwang, Areum Park, Chinwoo Kim, Danbi Yu, Hyungju Byun, Minhee Ku, Jaemoon Yang, Tae Il Kim, Kyu-Sung Jeong, Ki Young Kim, Hyuk Lee, Sang Joon Shin, Ku, Min Hee |
| بيانات النشر: | International Institute of Anticancer Research |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Animals, Apoptosis / drug effects, Autophagic Cell Death / drug effects, Autophagy / drug effects, Cell Line, Tumor, Cell Proliferation / drug effects, Cellular Reprogramming / genetics, Colorectal Neoplasms / drug therapy, Colorectal Neoplasms / genetics, Colorectal Neoplasms / pathology, Endoplasmic Reticulum / drug effects, Endoplasmic Reticulum / genetics, Endoplasmic Reticulum Stress / drug effects, Enzyme Inhibitors / pharmacology, Fluorouracil / pharmacology, Glycolysis / drug effects, Humans, Metabolic Networks and Pathways / drug effects, Mice, Protein Serine-Threonine Kinases / antagonists & inhibitors, Protein Serine-Threonine Kinases / genetics, Protein-Tyrosine Kinases / antagonists & inhibitors, Protein-Tyrosine Kinases / genetics, Reactive Oxygen Species / metabolism, Xenograft Model Antitumor Assays, DYRK1A protein, DYRK1B protein, autophagy, colorectal cancer |
| الوصف: | Background/aim: We previously identified KS40008 (4-(3-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)benzene-1,2-diol), a novel inhibitor of dual-specificity tyrosine phosphorylation-regulated kinase family (DYRK) 1A/B, which exhibited high enzymatic activity and cell proliferation-inhibitory effects in colorectal cancer (CRC) cell lines. In the present study, we aimed to elucidate the antitumor mechanisms of KS40008. Materials and methods: To assess the cytotoxicity of KS40008, we utilized a human cell line and organoid model and performed a CCK-8 assay and real-time cell analysis. Mitochondrial function was determined through mitochondrial staining, mito-stress test, and glycolysis test. In addition, we investigated the mechanisms of cancer cell death induced by KS40008 through immunoblotting, real-time quantitative polymerase chain reaction, reactive oxygen species staining, and immunofluorescence staining. Results: KS40008 exhibited significant cytotoxicity in CRC and non-CRC cell lines, and organoid models compared to 5-fluorouracil, a conventional chemotherapeutic drug. Moreover, KS40008-induced inhibition of DYRK1A/B led to mitochondrial dysfunction and endoplasmic reticulum stress, promoting autophagic cancer cell death. Conclusion: KS40008 exerts antitumor activity through the inhibition of DYRK1A/B. Here, we demonstrated a mechanism by which KS40008 affects endoplasmic reticulum stress-mediated autophagy through the induction of mitochondrial stress, leading to cytotoxicity in CRC. ; restriction |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0250-7005 1791-7530 |
| العلاقة: | ANTICANCER RESEARCH; J00188; OAK-2022-00168; https://ir.ymlib.yonsei.ac.kr/handle/22282913/187886Test; https://ar.iiarjournals.org/content/42/1/589.longTest; T202200213; ANTICANCER RESEARCH, Vol.42(1) : 589-598, 2022-01 |
| DOI: | 10.21873/anticanres.15516 |
| الإتاحة: | https://doi.org/10.21873/anticanres.15516Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/187886Test https://ar.iiarjournals.org/content/42/1/589.longTest |
| حقوق: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.7A9B20D5 |
| قاعدة البيانات: | BASE |
| تدمد: | 02507005 17917530 |
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| DOI: | 10.21873/anticanres.15516 |