# Role of Bisphenol A in the Development and Progression of Colorectal Cancer: Possible Sex-Specific Effects of Endogenous and Exogenous Estrogens

**Authors:** Elisabetta Iessi, Camilla Cittadini, Francesca Maranghi, Roberta Tassinari, Egidio Iorio, Rossella Puglisi, Gianfranco Mattia, Gianluca Frustagli, Lucia Coppola, Gabriele Lori, Cinzia La Rocca, Daniele Marcoccia, Marta Mollari, Flavia Silvia Galli, Maria Teresa Martino, Cosima Chiapperino, Laura Trilli, Pierpaolo Toto, Alessia Sgroi, Sara Di Matteo, Davide Brocco, Nicola Tinari, Elena Ortona, Paola Matarrese

PMC · DOI: 10.3390/biomedicines13112717 · 2025-11-05

## TL;DR

This study explores how bisphenol A and silibinin may affect colorectal cancer differently in men and women, focusing on estrogen-related mechanisms.

## Contribution

The study investigates sex-specific effects of BPA and SIL on colorectal cancer, combining multiple experimental approaches.

## Key findings

- BPA may have a pro-tumor role in colorectal cancer with potential gender differences.
- Silibinin may offer protective effects against colorectal cancer in both sexes.
- Estrogen and its receptors play a significant role in the onset and progression of colorectal cancer.

## Abstract

Background: Colorectal cancer (CRC) is more prevalent in men, and premenopausal women have a better prognosis than both men and postmenopausal women, suggesting a protective effect of estrogen. Humans are exposed to estrogen-like contaminants such as bisphenol A (BPA), a chemical used in the production of plastics that has been linked to hormone-related malignancies (e.g., breast, ovarian, and prostate cancers). The natural flavonolignan compound silibinin (SIL), acting as an estrogen agonist, may play a protective role in CRC in one or both sexes. Objectives: To explore the possible association between BPA and CRC, focusing on its potential pro-tumor role and possible gender differences. Analyzing the possible protective effects of SIL on the development of CRC is the secondary objective of the project. Methods: To shed light on the interaction between sex and estrogens, both endogenous and exogenous, in the onset of CRC. To this end, we combined ex vivo, in vitro, and in vivo approaches to deepen our understanding of the molecular mechanisms involved. Conclusions: The data provided by this study will contribute to understanding the role of estrogens and their receptors in the onset and progression of CRC and the potential protective role of SIL in both sexes.

## Linked entities

- **Chemicals:** bisphenol A (PubChem CID 6623), silibinin (PubChem CID 31553)
- **Diseases:** colorectal cancer (MONDO:0005575)

## Full-text entities

- **Diseases:** breast, ovarian, and prostate cancers (MESH:D010051), CRC (MESH:D015179), hormone-related malignancies (MESH:D009369)
- **Chemicals:** flavonolignan (MESH:D044947), SIL (MESH:D000077385), BPA (MESH:C006780)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12650405