Jolkinolide B inhibits glycolysis by downregulating hexokinase 2 expression through inactivating the Akt/mTOR pathway in non-small cell lung cancer cells.

Abstract

Jolkinolide B (JB), a bioactive compound isolated from herbal medicine, has been found to inhibit tumor growth by altering glycolysis. However, whether glycolysis is influenced by JB in non-small cell lung cancer (NSCLC) cells and the mechanism remain unknown. The aim of the present study was to evaluate the effect of JB on the glycolysis in NSCLC cells and the underlying molecular mechanism. The results showed that JB treatment inhibited cell viability of A549 and H1299 cells in a concentration-dependent manner. JB reduced the glucose consumption, lactate production, and HK2 expression. The expressions of p-Akt and p-mTOR were also decreased by JB treatment. Knockdown of HK2 reduced glucose consumption and lactate production. Inhibition of the Akt/mTOR pathway decreased HK2 expression and inhibited glycolysis. In conclusion, the results indicated that JB inhibits glycolysis by down-regulating HK2 expression through inactivating the Akt/mTOR pathway in NSCLC cells, suggesting that JB might be a potential therapeutic agent for the treatment of NSCLC.

• Authors: Xiang Gao, Han Han
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 119 Issue 6 Pg. 4967-4974 (06 2018) ISSN: 1097-4644 [Electronic] United States
• PMID: 29384225 (Publication Type: Journal Article)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Diterpenes
• jolkinolide B
• HK2 protein, human
• Hexokinase
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• A549 Cells
• Carcinoma, Non-Small-Cell Lung (enzymology, genetics, pathology)
• Diterpenes (pharmacology)
• Down-Regulation (drug effects)
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glycolysis (drug effects)
• Hexokinase (biosynthesis, genetics)
• Humans
• Lung Neoplasms (enzymology, genetics, pathology)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (genetics, metabolism)