# Sensitisation of HeLa Cell Cultures to Xanthone Treatment by RNAi-Mediated Silencing of NANOG and STAT3

**Authors:** Oliwia Gruszka, Dorota Żelaszczyk, Henryk Marona, Ilona Anna Bednarek

PMC · DOI: 10.3390/cimb47070529 · 2025-07-09

## TL;DR

This study shows that silencing specific genes in HeLa cells increases the effectiveness of xanthone-based cancer treatments.

## Contribution

RNAi-mediated silencing of NANOG and STAT3 enhances xanthone treatment efficacy in HeLa cells.

## Key findings

- Silencing NANOG and STAT3 increases HeLa cell sensitivity to xanthone treatment.
- Xanthones induce cytotoxicity and apoptosis in HeLa cells.
- ROS levels are affected by xanthone treatment and gene silencing.

## Abstract

The increasing morbidity of various types of cancer in the world’s population and the limited number of universal methods of their treatment contribute to the growth in research into the development of new treatment strategies. Most of this research focuses on treatments that target specific factors in cancer cell signalling pathways. There is also great interest in drugs derived from natural substances, as these represent one of the largest sources of potential pharmaceuticals. In our analysis, we focused on the action of α-mangostin and gambogic acid, which are natural xanthones or their synthetic derivatives. We studied their influence on the expression of STAT3 and NANOG, which play a confirmed role in different stages of cancer development. For this purpose, we applied RNAi-mediated gene silencing of NANOG and STAT3 to enhance the efficacy of xanthone-based anticancer treatment in HeLa cell cultures. After stimulating the cells with xanthones, we determined the expression of the tested transcription factors and the ROS level. In addition, we determined the cytotoxicity and apoptosis of the cells. Our research results confirm the anticancer efficacy of the analysed xanthones and demonstrate the role of the tested transcription factors. Silencing these factors makes cancer cells more susceptible to xanthone treatment.

## Linked entities

- **Genes:** NANOG (Nanog homeobox) [NCBI Gene 79923], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774]
- **Chemicals:** α-mangostin (PubChem CID 5281650), gambogic acid (PubChem CID 3451)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** NANOG (Nanog homeobox) [NCBI Gene 79923], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}
- **Diseases:** cancer (MESH:D009369), cytotoxicity (MESH:D064420)
- **Chemicals:** Xanthone (MESH:C009689), xanthones (MESH:D044004), ROS (-), alpha-mangostin (MESH:C021053), gambogic acid (MESH:C052659)
- **Cell lines:** HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12293224/full.md

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Source: https://tomesphere.com/paper/PMC12293224