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Lycorine hydrochloride interferes with energy metabolism to inhibit chemoresistant glioblastoma multiforme cell growth through suppressing PDK3.
Dong, Qingsheng; Niu, Wanxiang; Mu, Maolin; Ye, Chengkun; Wu, Pengfei; Hu, Shanshan; Niu, Chaoshi.
Afiliación
  • Dong Q; Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
  • Niu W; Department of Neurosurgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 17 Lujiang Road, Hefei, Anhui Province, 230027, People's Republic of China.
  • Mu M; Anhui Key Laboratory of Brain Function and Diseases, Hefei, Anhui, 230001, People's Republic of China.
  • Ye C; Department of Neurosurgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 17 Lujiang Road, Hefei, Anhui Province, 230027, People's Republic of China.
  • Wu P; Anhui Key Laboratory of Brain Function and Diseases, Hefei, Anhui, 230001, People's Republic of China.
  • Hu S; Department of Neurosurgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 17 Lujiang Road, Hefei, Anhui Province, 230027, People's Republic of China.
  • Niu C; Anhui Key Laboratory of Brain Function and Diseases, Hefei, Anhui, 230001, People's Republic of China.
Mol Cell Biochem ; 2024 Mar 11.
Article en En | MEDLINE | ID: mdl-38466468
ABSTRACT
Glioblastoma multiforme (GBM) is the highest grade of glioma. Tumours, including GBM, possess reprogrammed metabolism, such as altered aerobic glycolysis and aberrant energy production. Lycorine hydrochloride (LH) was extracted from the bulb of Lycoris radiata. The previous study indicated that LH exerts antiviral, anti-inflammatory and antitumour effects. However, the effect of LH on GBM and the underlying molecular mechanism remain unclear. Our study revealed that LH restrained chemoresistant GBM cells growth by inhibiting PDK3 expression in vitro and in vivo. Functionally, LH inhibited the proliferation and invasive capacity of chemoresistant GBM cells in dose-dependent manner. Metabolomics and cellular energy analyses showed that LH decreased extracellular acidification rates while increased oxidative respiration and ROS levels. Mechanistically, LH inhibits the growth of GBM chemoresistant cells by regulating the expression of apoptosis-related proteins, while overexpression of of PDK3 can reverse the antitumor effect of LH. In conclusion, our study revealed that LH could reprogramme cell energy metabolism, including aerobic glycolysis suppression and oxidative phosphorylation hyperactivation by inhibiting PDK3. PDK3 may be a candidate therapeutic target for chemoresistant GBM treatment with LH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Cell Biochem Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Cell Biochem Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos