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Apoptosis induced by sulindac sulfide in epithelial and mesenchymal cells from human abdominal neoplasms
L Picariello1, M L Brandi, L Formigli
1Department of Clinical Physiopathology, University of Florence, Italy.
Abstract:
We investigated whether the therapeutic action of sulindac, used for the treatment of familial adenomatous polyposis, desmoid tumors, and against colon cancer, could be mediated by its active metabolite, sulindac sulfide, in cell growth and apoptosis on cell lines derived from abdominal neoplasms. Sulindac sulfide actions on cell growth and apoptosis were evaluated in epithelial human colon tumor 8 (HCT8) cell line and mesenchymal cell lines (bovine bone endothelial (BBE) cell line, desmoid tumor-derived cells, human colorectal cancer-derived fibroblasts). Sulindac sulfide (0.1-60 microg/ml) induced a dose-dependent inhibition of cell proliferation of all cell lines tested. Apoptosis was induced at doses of 20 and 40 microg/ml, respectively, in BBE and HCT8 cells with no effect on desmoid tumor cells and colorectal cancer-derived fibroblasts. Since mesenchymal cells respond to clinically effective concentrations of the compound, its preferential action on the stromal compartment of intestinal polyps, desmoid tumors and colon cancer can be proposed, with consequent regression of the tumor.
Insights
Sulindac sulfide, a metabolite of sulindac, inhibits abdominal cancer cell growth. It also induces apoptosis in specific cancer cell types, suggesting a targeted therapeutic mechanism for colon cancer and desmoid tumors.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Sulindac is used to treat familial adenomatous polyposis, desmoid tumors, and colon cancer.
- The precise mechanism of sulindac's therapeutic action, particularly its metabolite sulindac sulfide, in abdominal neoplasms requires further elucidation.
Purpose of the Study:
- To investigate if sulindac sulfide mediates the therapeutic effects of sulindac.
- To evaluate the impact of sulindac sulfide on cell growth and apoptosis in various abdominal neoplasm-derived cell lines.
Main Methods:
- Sulindac sulfide's effects on cell proliferation and apoptosis were assessed in epithelial (HCT8) and mesenchymal (BBE, desmoid tumor-derived, colorectal cancer-derived fibroblasts) cell lines.
- Dose-dependent responses to sulindac sulfide (0.1-60 microg/ml) were analyzed.
Main Results:
- Sulindac sulfide demonstrated a dose-dependent inhibition of cell proliferation across all tested cell lines.
- Apoptosis was induced in BBE and HCT8 cells at specific concentrations (20 and 40 microg/ml, respectively).
- No significant effect on apoptosis was observed in desmoid tumor cells and colorectal cancer-derived fibroblasts.
Conclusions:
- Sulindac sulfide exhibits anti-proliferative effects on various abdominal cancer cell types.
- The induction of apoptosis in specific cell lines suggests a targeted mechanism for sulindac's therapeutic action.
- Preferential action on mesenchymal cells at clinically relevant concentrations supports its role in the stromal compartment of tumors, potentially leading to regression.