Prophylactic effects of triptolide on colon cancer development in azoxymethane/dextran sulfate sodiuminduced mouse model
Purpose: To investigate effects of triptolide on colon cancer cell growth and its capacity to prevent tumor development in an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of colon cancer.
Methods: HCT116 cell viability and migration potential were assessed. Control and AOM/DSS-treated mice (with and without triptolide) were analyzed for tumor development. The animals were divided into five groups (n = 5). Normal control group was given saline, animals in the untreated control group received AOM and DSS while animals in the treatment groups received 10, 50 and 100 mg/kg doses of triptolide intraperitoneally alternately for 2 months after AOM and DSS injection.
Results: Triptolide enhanced nuclear material condensation, significantly (p < 0.05) increased the levels of cleaved poly (ADP-ribose) polymerase, reduced the levels of pro-caspase-3 and pro-caspase-8 in HCT116 cells. Triptolide also significantly (p < 0.05) decreased the expression of pIκBα, activated peroxisome proliferator-activated receptor γ, and markedly reduced the activity of both metalloproteinase-2 and metalloproteinase-9. Treatment of AOM/DSS mice with triptolide significantly reduced adenocarcinoma multiplicity compared to the control group.
Conclusion: Triptolide administration suppresses growth of HCT116 cells and colon cancer development in mice by inhibiting inflammatory responses. Therefore, triptolide has potentials to be developed for colon cancer therapy.
Keywords: Cell viability, Condensation, Metalloproteinase, Apoptotic, Triptolide, Adenocarcinoma, Colon cancer