Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 69, Issue 45, Pages 13557-13567Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c05394
Keywords
cynaropicrin; pyruvate kinase M2; cell cycle arrest; mitochondrial damage; apoptosis
Funding
- National Natural Science Foundation of China [21778028, 22077055]
- Natural Science Foundation of Gansu Province [20JR5RA311, 18JR4RA003]
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The research demonstrates that CYN inhibits PKM2 activity and induces cell cycle arrest, oxidative stress, and mitochondrial damage. However, overexpression of PKM2 attenuates the effects of CYN on cells.
Metabolic reprogramming is critical for tumorigenesis. Pyruvate kinase M2 (PKM2) is overexpressed in lung carcinoma cells and plays a critical role in the Warburg effect, making the enzyme a research hotspot for anticancer drug development. Cynaropicrin (CYN), a natural sesquiterpene lactone compound from artichoke, has received increasing consideration due to its consumable esteem and pharmacological properties. Our data reveal that CYN not only inhibited the purified PKM2 activity but also decreased the cellular PKM2 expression in A549 cells. The inhibition of PKM2 leads to the upregulation of p53 and the downregulation of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP), and subsequently causes the cell cycle arrest. Additionally, CYN inhibits the interaction of PKM2 and Nrf2, resulting in the impairment of cellular antioxidant capacity, induction of oxidative stress, and mitochondrial damages. Overexpression of PKM2 attenuates the CYN-induced DNA damage, mitochondrial fission, and cell viability. Thus, targeting PKM2 provides an original mechanism for understanding the pharmacological impact of CYN and assists in the further development of CYN as an anticancer agent.
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