Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2021; 27(14): 1435-1450
Published online Apr 14, 2021. doi: 10.3748/wjg.v27.i14.1435
Cyanidin 3-glucoside modulated cell cycle progression in liver precancerous lesion, in vivo study
Marwa Matboli, Amany H Hasanin, Reham Hussein, Sarah El-Nakeep, Eman K Habib, Rawan Ellackany, Lobna A Saleh
Marwa Matboli, Department of Biochemistry, Ain Shams Faculty of Medicine, Cairo 11318, Egypt
Amany H Hasanin, Reham Hussein, Lobna A Saleh, Department of Clinical Pharmacology, Ain Shams Faculty of Medicine, Cairo 11381, Egypt
Sarah El-Nakeep, Department of General Internal Medicine, Ain Shams Faculty of Medicine, Cairo 11381, Egypt
Eman K Habib, Department of Anatomy & Embryology, Ain Shams Faculty of Medicine, Cairo 11318, Egypt
Rawan Ellackany, Department of Undergraduate, Faculty of Medicine, Modern University for Technology and Information, Cairo 11381, Egypt
Author contributions: Matboli M and Hasanin AH conceived the presented idea, developed the theory; Matboli M performed the statistics and the molecular assay; Hasanin AH verified the analytical methods; Hussein R and Saleh LA carried out the experimental animal work, performed the statistical analysis, writing the manuscript; El-Nakeep S developed the theory and writing the manuscript; Ellackany R has shared in the revision of the manuscript; Habib EK performed the histopathological examination and writing the comments; all authors discussed the results and contributed to the final manuscript revision.
Institutional animal care and use committee statement: All animal procedures were approved by the Institutional Animal Ethics Committee for Ain Shams University, Faculty of Medicine.
Conflict-of-interest statement: No competing interest.
Data sharing statement: Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Marwa Matboli, MD, Associate Professor, Department of Biochemistry, Ain Shams Faculty of Medicine, Abassia Marg, Cairo 11318, Egypt.
Received: December 22, 2020
Peer-review started: December 22, 2020
First decision: January 17, 2021
Revised: January 22, 2021
Accepted: March 26, 2021
Article in press: March 26, 2021
Published online: April 14, 2021

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.


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.


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.


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.


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

Core Tip: Several regulatory RNA networks are important in regulation of liver cell cycle progression and are linked to the pathogenesis of hepatocellular carcinoma. Identification of critical steps involved in hepatocarcinogenesis are likely to lead to the development of new therapeutics that will inhibit tumor proliferation alongside with verification of promising drug targets biomarkers that may lead to improved patient survival. Cyanidin-3-O-glucoside (cyan) has a significant antioxidant and anticancer activities. Cyan could be used as potential agent to inhibit liver carcinogenesis in rat model via modulation of cell cycle. Cyan dose dependently decreased the long non-coding RNA-MALAT1 and tubulin 1 mRNA expressions and increased the hsa-miR-125b expression which participate in cell cycle and mitotic spindle assembly.