Mechanism of Action of Cyanidin 3-O-Glucoside in Gluconeogenesis and Oxidative Stress-Induced Cancer Cell Senescence

Yaoyao Jia, Chunyan Wu, Adriana Rivera-Piza, Yeon Ji Kim, Ji Hae Lee, Sung Joon Lee

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin abundant in fruits and vegetables that interacts and possibly modulates energy metabolism and oxidative stress. This study investigated the effect of C3G on gluconeogenesis and cancer cell senescence. C3G activates adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor involved in metabolism and the aging process. C3G suppressed hepatic gluconeogenesis by reducing the expression of gluconeogenic genes through the phosphorylation inactivation of CRTC2 and HDAC5 coactivators via AMPK. C3G did not directly interact with AMPK but, instead, activated AMPK through the adiponectin receptor signaling pathway, as demonstrated through adiponectin receptor gene knock-down experiments. In addition, C3G increased cellular AMP levels in cultured hepatocytes, and the oral administration of C3G in mice elevated their plasma adiponectin concentrations. These effects collectively contribute to the activation of AMPK. In addition, C3G showed potent antioxidant activity and induced cellular senescence, and apoptosis in oxidative-stress induced senescence in hepatocarcinoma cells. C3G increased senescence-associated β-galactosidase expression, while in-creasing the expression levels of P16, P21 and P53, key markers of cellular senescence. These findings demonstrate that anthocyanin C3G achieves hypoglycemic effects via AMPK activation and the subsequent suppression of gluconeogenesis and exhibits anti-cancer activity through the induction of apoptosis and cellular senescence.

Original languageEnglish
Article number749
Issue number4
Publication statusPublished - 2022 Apr

Bibliographical note

Funding Information:
Funding: This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (Grant Nos. NRF-2019R1A2C3005227) and a Korea University Grant.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • Cyanidin 3-O-Glucoside
  • HepG2 cells
  • adiponectin signaling
  • anti-carcinogenic activity
  • antioxidants
  • hepatic autophagy
  • natural products
  • oxidative stress
  • phytochemicals

ASJC Scopus subject areas

  • Food Science
  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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