Published online Apr 14, 2021. doi: 10.3748/wjg.v27.i14.1435
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.
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.