# GATA4-targeted compounds induce apoptosis and diminish viability of hepatoblastoma cells

## TL;DR

A new compound targeting GATA4 reduces the survival of liver tumor cells in children by disrupting their cell cycle.

## Contribution

A novel GATA4-targeted compound (3i-2012) is shown to effectively reduce hepatoblastoma cell viability and alter cell cycle regulation.

## Key findings

- 3i-2012 was the most effective compound in reducing hepatoblastoma cell viability.
- 3i-2012 induced G0/G1 cell cycle arrest and increased caspase activity in tumor cells.
- Differentially expressed genes linked to cell cycle regulation were likely regulated by GATA4.

## Abstract

Hepatoblastoma is the most common pediatric liver tumor, and it primarily affects young children. Despite improved treatment results due to modern chemotherapy and advanced surgical techniques, there is urgent need to improve the long-term prognosis of hepatoblastoma patients. Elevated expression of transcription factor GATA4 has been associated with pro-tumorigenic functions in hepatoblastoma. Herein, we explored the effects of a novel series of GATA4-targeted compounds (3i-2010–3i-2014) in several hepatoblastoma cell models. To this end, we assessed cell viability (2D and 3D), caspase 3/7 activity, cell cycle process with automated fluorescence microscopy, and RNA and protein expression using quantitative PCR, RNA-sequencing, and western blotting after treating cells with GATA4-targeted compounds. The GATA4-targeted compounds reduced hepatoblastoma cell viability but affected also healthy control cells when high doses were applied. Out of the five compounds used, the 3i-2012 was the most potent. This compound induced G0/G1 phase cell cycle arrest, increased caspase activity, and resulted in changes in transcriptome of hepatoblastoma cells. The differentially expressed genes (DEGs) were associated with cell cycle regulation. Transcription factor target analysis demonstrated that a notable proportion of DEGs were likely regulated by GATA4. In conclusion, 3i-2012 decreases hepatoblastoma cell survival by disturbing cell cycle regulation in the tumor cells.