Cyanidin 3-glucoside modulated cell cycle progression in liver precancerous lesion, in vivo study

World J Gastroenterol. 2021 Apr 14;27(14):1435-1450. doi: 10.3748/wjg.v27.i14.1435.

Abstract

Background: Cyanidin-3-O-glucoside (cyan) exhibits antioxidant and anticancer properties. The cell cycle proteins and antimitotic drugs might be promising therapeutic targets in hepatocellular carcinoma.

Aim: To investigate the effect of cyan administration on cell cycle in hepatic precancerous lesion (PCL) induced by diethylnitrosamine/2-acetylaminofluorene (DEN/2-AAF) in Wistar rats.

Methods: In vivo, DEN/2-AAF-induced hepatic PCL, rats were treated with three doses of cyan (10, 15, and 20 mg/kg/d, for four consecutive days per week for 16 wk). Blood and liver tissue samples were collected for measurement of the followings; alpha fetoprotein (AFP) liver function and RNA panel differential expression was evaluated via real time polymerase chain reaction. Histopathological examination of liver sections stained with H&E and immunohistochemical study using glutathione S-transferase placental (GSTP) and proliferating cell nuclear antigen (PCNA) antibodies were assessed.

Results: Cyan administration mitigated the effect of DEN/2-AFF induced PCL, decreased AFP levels, and improved liver function. Remarkably, treatment with cyan dose dependently decreased the long non-coding RNA MALAT1 and tubulin gamma 1 mRNA expressions and increased the levels of miR-125b, all of which are involved in cell cycle and mitotic spindle assembly. Of note, cyan decreased GSTP foci percent area and PCNA positively stained nuclei.

Conclusion: Our results indicated that cyan could be used as a potential therapeutic agent to inhibit liver carcinogenesis in rat model via modulation of cell cycle.

Keywords: Hepatocellular carcinoma therapy; Hepatocellular-carcinoma growth; Hepatocellular-carcinoma model; Hepatocellular-carcinoma size.

MeSH terms

  • Animals
  • Anthocyanins
  • Diethylnitrosamine / toxicity
  • Female
  • Glucosides / pharmacology
  • Glutathione Transferase
  • Liver
  • Liver Neoplasms*
  • Liver Neoplasms, Experimental* / chemically induced
  • Liver Neoplasms, Experimental* / drug therapy
  • Precancerous Conditions* / chemically induced
  • Precancerous Conditions* / drug therapy
  • Pregnancy
  • Rats
  • Rats, Wistar

Substances

  • Anthocyanins
  • Glucosides
  • Diethylnitrosamine
  • cyanidin
  • Glutathione Transferase