# Riboflavin (VB2) inhibits hepatocellular carcinogenesis by enhancing retinol metabolism and suppressing cell proliferation in Hras12V transgenic mice

## TL;DR

Riboflavin (VB2) can prevent liver cancer in mice by boosting retinol metabolism and slowing cell growth.

## Contribution

This is the first in vivo study showing riboflavin alone suppresses liver tumor formation.

## Key findings

- VB2 reduced liver tumor burden and improved liver histology in transgenic mice.
- VB2 enhanced retinol metabolism and inhibited cell proliferation via p21 and Mcm complex.
- VB2 showed limited but notable inhibitory effects on established tumors.

## Abstract

Riboflavin (VB2) is primarily utilized as an adjuvant in cancer therapy. This study aims to investigate the preventive and therapeutic effects of VB2 alone on hepatocellular carcinoma (HCC).

The preventive and therapeutic efficacy of VB2 against HCC was evaluated using a Hras12V transgenic mouse model of HCC. Initial mechanistic insights were obtained through transcriptome sequencing combined with bioinformatic analyses, and key findings were validated via molecular biology techniques.

VB2 administration significantly suppressed hepatic tumorigenesis, as evidenced by reductions in liver tumor burden and improved histology. Bioinformatic analysis revealed that VB2-mediated tumor suppression may involve the regulation of multiple metabolic pathways, including fatty acid and amino acid metabolism. Subsequent molecular validation indicated that VB2 enhanced hepatic retinol metabolism by upregulating key metabolic enzymes. It concurrently inhibited hepatocellular proliferation through p21-mediated G1/S phase arrest and suppressed DNA replication by downregulating the Mcm helicase complex. Additionally, VB2 exhibited inhibitory activity against the progression of established tumors, although this effect was not as significant as its suppression of hepatic tumorigenesis. Safety assessments in wild-type C57BL/6 mice revealed no significant treatment-related toxicity.

To our knowledge, this study is the first to demonstrate in vivo that VB2 alone can significantly suppress hepatic tumorigenesis by enhancing retinol metabolism and inhibiting cell proliferation pathways, highlighting its potential as a chemopreventive agent for HCC.