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Drug evaluation based on phosphomimetic PDHA1 reveals the complexity of activity-related cell death in A549 non-small cell lung cancer cells.
Jin, Ling; Cho, Minkyoung; Kim, Bo-Sung; Han, Jung Ho; Park, Sungmi; Lee, In-Kyu; Ryu, Dongryeol; Kim, Jae Ho; Bae, Sung-Jin; Ha, Ki-Tae.
Afiliación
  • Jin L; Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612; Korean Medical Research Center for Healthy Aging, Pusan National University, Yangsan 50612, Korea.
  • Cho M; Korean Medical Research Center for Healthy Aging, Pusan National University, Yangsan 50612, Korea.
  • Kim BS; Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612; Korean Medical Research Center for Healthy Aging, Pusan National University, Yangsan 50612, Korea.
  • Han JH; Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612; Korean Medical Research Center for Healthy Aging, Pusan National University, Yangsan 50612, Korea.
  • Park S; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
  • Lee IK; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, 4Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41404, Korea.
  • Ryu D; Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Suwon 16419, Korea.
  • Kim JH; Department of Physiology, College of Medicine, Pusan National University, Yangsan 50612, Korea.
  • Bae SJ; Korean Medical Research Center for Healthy Aging, Pusan National University, Yangsan 50612, Korea.
  • Ha KT; Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan 50612; Korean Medical Research Center for Healthy Aging, Pusan National University, Yangsan 50612, Korea.
BMB Rep ; 54(11): 563-568, 2021 Nov.
Article en En | MEDLINE | ID: mdl-34488935
Cancer cells predominantly generate energy via glycolysis, even in the presence of oxygen, to support abnormal cell proliferation. Suppression of PDHA1 by PDK1 prevents the conversion of cytoplasmic pyruvate into Acetyl-CoA. Several PDK inhibitors have been identified, but their clinical applications have not been successful for unclear reasons. In this study, endogenous PDHA1 in A549 cells was silenced by the CRISPR/Cas9 system, and PDHA1WT and PDHA13SD were transduced. Since PDHA13SD cannot be phosphorylated by PDKs, it was used to evaluate the specific activity of PDK inhibitors. This study highlights that PDHA1WT and PDHA13SD A549 cells can be used as a cell-based PDK inhibitor-distinction system to examine the relationship between PDH activity and cell death by established PDK inhibitors. Leelamine, huzhangoside A and otobaphenol induced PDH activity-dependent apoptosis, whereas AZD7545, VER-246608 and DCA effectively enhanced PDHA1 activity but little toxic to cancer cells. Furthermore, the activity of phosphomimetic PDHA1 revealed the complexity of its regulation, which requires further in-depth investigation. [BMB Reports 2021; 54(11): 563-568].
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Piruvato Deshidrogenasa (Lipoamida) / Evaluación de Medicamentos / Inhibidores Enzimáticos / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: BMB Rep Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2021 Tipo del documento: Article Pais de publicación: Corea del Sur
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Piruvato Deshidrogenasa (Lipoamida) / Evaluación de Medicamentos / Inhibidores Enzimáticos / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: BMB Rep Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2021 Tipo del documento: Article Pais de publicación: Corea del Sur