Abstract: FR-PO223
P-cresyl Sulfate and Indoxyl Sulfate: Uremic Toxins Implicated in the Progression of Colorectal Cancer in Individuals with CKD
Session Information
- Onconephrology: Immunotherapy Nephrotoxicity and Assessment of GFR
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Simeoni, Mariadelina, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
- Di Paola, Rossella, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
- Trevisani, Francesco, San Raffaele Scientific Institute,, Milan, Italy
- Abate, Marianna, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
- Perna, Alessandra, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
- Zappavigna, Silvia, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
- Cossu, Alessia Maria, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
- Bocchetti, Marco, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
- Melisi, Federica, Biogem Scarl, Ariano Irpino, Italy
- Iannarone, Clara, Biogem Scarl, Ariano Irpino, Italy
- Pasquale, Lucia Stefania, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
- Scrima, Marianna, Biogem Scarl, Ariano Irpino, Italy
- Caraglia, Michele, Universita degli Studi della Campania Luigi Vanvitelli, Caserta, Italy
Background
Patients with chronic kidney disease (CKD) have a higher incidence of colorectal cancer (CRC) and a significantly poorer prognosis compared to the general population. The reasons for this are not yet understood. One common issue in CKD patients is gut dysbiosis, which is marked by an excess of aerobic bacteria in the gut microbiota. Their metabolic activity results mainly in two metabolites: P-cresyl sulfate (P-cs) and Indoxyl sulfate (IS). Many studies indicate that these metabolites are instrumental in triggering various cancer-causing processes, such as chronic intestinal inflammation and oxidative stress. Given the cancer-promoting effects of P-cs and IS in CKD patients, it appears plausible that these toxins could play a significant role in the advancement of CRC in these individuals.
Methods
To assess the impact of IS and P-cs on three CRC cell lines (Hct116, LoVo, and HT-29), we conducted a range of in vitro experiments. We examined various concentrations of IS and P-cs and used a WST 8 to measure their influence on cancer cell proliferation. We subsequently applied the Wound Healing Assay and invasion assay to evaluate the migratory and invasive abilities of CRC cells after exposure to the toxins. To identify the pathways altered by the toxins, we performed qPCR and ROS assay experiments to assess the inflammatory pathway and the production of ROS.
Results
We noted an enhancement in cell growth following the treatment with toxins. Moreover, the concentrations of IS and P-cs triggered a significant escalation in cell migration and invasion. An examination of the expression of genes linked to the inflammatory process (INOS and IL-6) revealed an increased regulation of the latter across all cell lines. Lastly, a rise in oxidative stress was also detected in the cells treated with toxins when compared to the control group.
Conclusion
From our findings, it seems that IS and P-cs significantly contribute in vitro to the advancement of CRC. Future investigations in translational studies are needed to explore whether these conclusions can be extended to CKD patients with CRC, also exploring potential new target therapies and diagnostic tools
Funding
- Government Support – Non-U.S.