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Polyphyllin II Induces Apoptosis in Fibrosarcoma Cells via Activating Pyruvate Kinase M2.
Wu, Jun; Ding, Zhenjiang; Zhong, Miao; Xi, Junmin; He, Ying; Zhang, Baoxin; Fang, Jianguo.
Afiliação
  • Wu J; State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
  • Ding Z; Beijing Key Laboratory of the Innovative Development of Functional Staple and Nutritional Intervention for Chronic Diseases, China National Research Institute of Food and Fermentation Industries, Beijing 100015, China.
  • Zhong M; State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
  • Xi J; State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
  • He Y; State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
  • Zhang B; State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
  • Fang J; School of Chemistry and Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094 , Jiangsu, China.
Chem Res Toxicol ; 37(8): 1394-1403, 2024 Aug 19.
Article em En | MEDLINE | ID: mdl-39066737
ABSTRACT
Aerobic glycolysis is a metabolic reprogramming of tumor cells that is essential for sustaining their phenotype of fast multiplication by continuously supplying energy and mass. Pyruvate kinase M2 (PKM2) has a vital role in this process, which has given it high interest as a target for anticancer drug development. With potent toxicity to many types of cancer cells, polyphyllin II (PP2), a steroidal saponin isolated from the herbaceous plant Rhizoma paridis, brought to our attention that it might interfere with the PKM2 activity. In this study, we discovered that PP2 was a novel agonist of PKM2. PP2 activated recombinant PKM2 and changed the protein's oligomeric state to activate intracellular PKM2. At the same time, PP2 suppressed its protein kinase function by decreasing the content of nuclear PKM2. The mRNA levels of its downstream genes, such as Glut1, LDHA, and MYC, were inhibited. In addition, PP2 induced oxidative stress by downregulating the expression and activity of antioxidant proteins such as NQO1, TrxR, and Trx in HT-1080 cells, which in turn led to mitochondrial dysfunction and ultimately induced apoptosis. Moreover, PP2 reduced the proliferation and migration of HT-1080 cells. Thus, targeting the glycolysis pathway offers an unprecedented mode of action for comprehending PP2's pharmacological impacts and advances PP2's further development in fibrosarcoma therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piruvato Quinase / Saponinas / Apoptose Limite: Humans Idioma: En Revista: Chem Res Toxicol Assunto da revista: TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piruvato Quinase / Saponinas / Apoptose Limite: Humans Idioma: En Revista: Chem Res Toxicol Assunto da revista: TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos