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KMU-191 Induces Apoptosis in Human Clear Cell Renal Cell Carcinoma Caki Cells Through Modulation of Bcl-xL, Mcl-1 (L), c-FLIP (L), and p53 Proteins.
Kim, Shin; Kim, Dong Eun; Kang, Hyunsu; Hong, Victor Sukbong; Jeon, Jieun; Lee, Jinho; Kim, Ki-Suk; Park, Jong-Wook.
Afiliación
  • Kim S; Department of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Republic of Korea.
  • Kim DE; Institute of medical science, Keimyung University, School of Medicine, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Republic of Korea.
  • Kang H; Institute for Cancer Research, Keimyung University, School of Medicine, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Republic of Korea.
  • Hong VS; Department of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Republic of Korea.
  • Jeon J; R&D Center for Advanced Pharmaceuticals & Evaluation, Korea Institute of Toxicology, Daejeon 34114, Korea.
  • Lee J; Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea.
  • Kim KS; Department of Chemistry, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Republic of Korea.
  • Park JW; Department of Immunology, School of Medicine, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Republic of Korea.
J Cancer ; 14(12): 2224-2235, 2023.
Article en En | MEDLINE | ID: mdl-37576393
The anti-proliferative effects of a newly developed N3-acyl-N5-aryl-3,5-diaminoindazole analog, KMU-191, have been previously evaluated in various cancer cells. However, the detailed anti-cancer molecular mechanisms of KMU-191 remain unknown. In this study, we investigated anti-cancer mechanisms by which KMU-191 regulates apoptosis-related genes in human clear cell renal cell carcinoma Caki cells. KMU-191 induced poly ADP-ribose polymerase cleavage and caspase-dependent apoptosis. In addition, KMU-191 induced down-regulation of the long form of cellular FADD-like IL-1ß-converting enzyme inhibitory protein (c-FLIP (L)) at the transcriptional level as well as that of long form of myeloid cell leukemia (Mcl-1 (L)) and B-cell lymphoma-extra large at the post-transcriptional level. Furthermore, KMU-191-induced apoptosis was closely associated with the Mcl-1 (L) down-regulation, but also partially associated with c-FLIP (L) down-regulation. In contrast, KMU-191 up-regulated p53, which is closely related to KMU-191-induced apoptosis. Although KMU-191 showed cytotoxicity of normal cells, it unusually did not induce cardiotoxicity. Taken together, these results suggest that a multi-target small molecule, N3-acyl-N5-aryl-3,5-diaminoindazole analog, KMU-191 is a potential anti-cancer agent that does not induce cardiotoxicity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cancer Año: 2023 Tipo del documento: Article Pais de publicación: Australia
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cancer Año: 2023 Tipo del documento: Article Pais de publicación: Australia