Synergistic effects in apoptosis induction by taurolidine and TRAIL in HCT-15 colon carcinoma cells
A M Chromik1, A Daigeler, C Hilgert
1Department of Visceral and General Surgery, St. Josef Hospital, Ruhr-University, Bochum, Germany. a. chromik@klinikum-bochum.de
Abstract:
Induction of apoptosis in tumor cells by TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) is a promising therapeutic principle in oncology, although toxicity and resistance against TRAIL are limiting factors. Taurolidine (TRD), an antineoplastic agent with low toxicity, is a potential candidate for combined therapy with TRAIL. The aim of this study was to evaluate the apoptotic effects of a combined treatment with TRD and TRAIL in a human HCT-15 colon carcinoma cell line. HCT-15 cells were incubated with increasing concentrations of recombinant human TRAIL (50 ng/mL to 500 ng/mL) or TRD (50 micromol/L to 1000 micromol/L). In a second experiment, cells were furthermore exposed to a combination of both substances (TRAIL 50 ng/mL and TRD 100 micromol/L). At various time points (3 h to 36 h), cell viability, apoptosis, and necrosis were quantified by FACS analysis (propidium iodide/annexin V-FITC) and confirmed by TUNEL assay. Incubation with TRD resulted in cell death induction with maximum effects observed at 100 micromol/L and 1000 micromol/L after 36 h. TRAIL application led to dose-dependent cell death induction as early as 6 h. Combined treatment of TRD (100 micromol/L) and TRAIL (50 ng/mL) caused a sustained induction of apoptosis that was superior to single-agent application, exceeding a merely additive effect. Combinatory treatment of human colon carcinoma cells with TRD and TRAIL results in a synergistic effect on apoptosis induction with a significant increase of the apoptotic index. Combination of TRAIL with the nontoxic TRD might represent a novel therapeutic strategy in oncological therapy.
Insights
Combining taurolidine (TRD) with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) synergistically enhances apoptosis in colon cancer cells. This novel combination therapy shows promise for improved oncological treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) induces apoptosis in tumor cells, but its therapeutic use is limited by toxicity and resistance.
- Taurolidine (TRD) is an antineoplastic agent with low toxicity, making it a potential candidate for combination therapy.
Purpose of the Study:
- To evaluate the combined apoptotic effects of TRD and TRAIL in a human HCT-15 colon carcinoma cell line.
- To determine if TRD and TRAIL combination therapy offers synergistic effects on apoptosis induction.
Main Methods:
- HCT-15 colon carcinoma cells were treated with varying concentrations of TRAIL and TRD, individually and in combination.
- Cell viability, apoptosis, and necrosis were quantified using FACS analysis and TUNEL assay at multiple time points.
Main Results:
- TRD induced cell death, with maximum effects observed at 100 and 1000 micromol/L after 36 hours.
- TRAIL induced dose-dependent cell death starting at 6 hours.
- The combination of TRD (100 micromol/L) and TRAIL (50 ng/mL) resulted in sustained apoptosis induction superior to single-agent treatments, demonstrating a synergistic effect.
Conclusions:
- Combined treatment of human colon carcinoma cells with TRD and TRAIL induces apoptosis synergistically.
- This combination therapy significantly increases the apoptotic index.
- The combination of TRAIL with non-toxic TRD represents a novel therapeutic strategy in oncology.
