# Harnessing Postbiotics to Boost Chemotherapy: N-Acetylcysteine and Tetrahydro β-Carboline Carboxylic Acid as Potentiators in Pancreatic and Colorectal Cancer

## TL;DR

This study explores how gut-derived postbiotics like N-acetylcysteine and tetrahydro β-carboline carboxylic acid may help improve chemotherapy for pancreatic and colorectal cancer by reducing cancer cell growth and enhancing drug effects.

## Contribution

The study introduces two postbiotics as potential chemotherapy potentiators for pancreatic and colorectal cancer through in vitro experiments.

## Key findings

- N-acetylcysteine and tetrahydro β-carboline carboxylic acid reduced cancer cell growth in pancreatic and colorectal cancer models.
- Tetrahydro β-carboline carboxylic acid showed stronger anticancer effects than N-acetylcysteine across all tested cell lines.
- Combining postbiotics with chemotherapy drugs enhanced drug effectiveness in certain cancer cell types.

## Abstract

Chemotherapy is widely used to treat cancer, but its effectiveness can be limited by drug resistance and side effects. In recent years, compounds produced by our gut bacteria, also known as postbiotics, have gained attention for their potential to support cancer treatment. In this study, we investigated whether two postbiotics, N-acetylcysteine and tetrahydro β-carboline carboxylic acid, could influence the growth of pancreatic and colorectal cancer cells. We tested their effects on cell survival, cell cycle regulation, and programmed cell death, both alone and in combination with common chemotherapy drugs. Our results showed that both postbiotics reduced cancer cell growth, with tetrahydro β-carboline carboxylic acid showing particularly strong effects. When combined with chemotherapy, both postbiotics enhanced the anticancer activity of the drugs in certain cell types. These findings provide preliminary in vitro evidence suggesting that postbiotics may serve as potential adjuvants to chemotherapy.

Background: Pancreatic cancer (PC) and colorectal cancer (CRC) are among the most lethal malignancies, with growing evidence pointing to the gut microbiota’s role in their progression. This study aimed to explore the anticancer potential of two microbiota-derived postbiotics, N-acetylcysteine (NAC) and tetrahydro β-carboline carboxylic acid (THC), in targeting some hallmark traits of PC and CRC, both as standalone agents and in combination with standard chemotherapeutics (gemcitabine for PC and 5-fluorouracil (5-FU) for CRC). Methods: Cell viability assays and IC50 determination was assessed using either the Muse™ Count & Viability Kit or the Sulforhodamine B assay; cell death was determined by Annexin V/Propidium Iodide and cell cycle assessed by Propidium Iodide was analyzed by flow cytometry. Results: Here, we found that NAC selectively reduced the viability of PC cells BxPC-3 without triggering apoptosis, while effectively inducing apoptosis in PC cells Panc-1 and in CRC cell lines. THC exhibited stronger anticancer activity, inhibiting proliferation and promoting apoptosis in all tested PC and CRC cells, even at lower concentrations. Combination treatments yielded promising enhancement effects. NAC enhanced the cytotoxicity of gemcitabine in Panc-1 cells through increased apoptosis. NAC, when combined with 5-FU, also increased apoptosis of CRC cells. THC further potentiated gemcitabine’s impact on Panc-1 cells by increasing apoptosis and by inducing cell cycle changes in BxPC-3. In the CRC model, THC co-treatment with 5-FU reduced cell viability and increased apoptosis in all cells. Conclusions: These findings provide preliminary in vitro evidence supporting the potential of integrating microbiota-derived postbiotics with conventional chemotherapy both in PC and CRC.