The Mixture of Ferulic Acid and P-Coumaric Acid Suppresses Colorectal Cancer through lncRNA 495810/PKM2 Mediated Aerobic Glycolysis

Polyphenol-rich foods are gaining popularity due to their potential beneficial effects in the prevention and treatment of cancer. Foxtail millet is one of the important functional foods, riches in a variety of biologically active substance. Our previous study showed that ferulic acid (FA) and p-coum...

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Published inInternational journal of molecular sciences Vol. 23; no. 20; p. 12106
Main Authors Cui, Kaili, Wu, Haili, Fan, Jiangming, Zhang, Lichao, Li, Hanqing, Guo, Huiqin, Yang, Ruipeng, Li, Zhuoyu
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 11.10.2022
MDPI
Subjects
Acids
aerobic glycolysis
Biological activity
Cancer
Cancer therapies
Cereals
Colorectal cancer
Colorectal carcinoma
Coumaric acid
Cytotoxicity
Drug dosages
Enzymes
Ferulic acid
Functional foods & nutraceuticals
Glucose
Glycolysis
lncRNA 495810
Metabolism
Millet
Non-coding RNA
p-Coumaric acid
PKM2
polyphenol
Polyphenols
Pyruvate kinase
Pyruvic acid
Synergistic effect
China
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Summary:Polyphenol-rich foods are gaining popularity due to their potential beneficial effects in the prevention and treatment of cancer. Foxtail millet is one of the important functional foods, riches in a variety of biologically active substance. Our previous study showed that ferulic acid (FA) and p-coumaric acid (p-CA) are the main anticancer components of foxtail millet bran, and the two have a significant synergistic effect. In the present study, the clinical application potential of FA and p-CA (FA + p-CA) were evaluated in vivo and in vitro. The FA and p-CA target gene enrichment analysis discovered that FA + p-CA were associated with aerobic glycolysis. It was further shown that FA + p-CA remodel aerobic glycolysis by inhibiting the glycolysis-associated lncRNA 495810 and the glycolytic rate-limiting enzyme M2 type pyruvate kinase (PKM2). Moreover, PKM2 expression was positively correlated with lncRNA 495810. More interestingly, the exogenous expression of lncRNA 495810 eliminated the inhibitory effects of FA + p-CA on aerobic glycolysis. Collectively, FA + p-CA obstruct the aerobic glycolysis of colorectal cancer cells via the lncRNA 495810/PKM2 axis, which provides a nutrition intervention and treatment candidate for colorectal cancer.
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These authors contributed equally to this work.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms232012106