TPEN

Description: TPEN (also known as TPED) is a specific cell-permeable heavy metal chelator. TPEN targets colon cancer cells through redox cycling of copper. TPEN reduced cell viability in a dose- and time-dependent manner. Cytotoxicity was associated with significant DNA damage and higher expression of gamma-H2AX protein and activation of ATM/ATR signaling pathway. Cell death by TPEN was dependent on ROS generation as evidenced by the reversal of cell viability, and DNA damage and the abrogation of gamma-H2AX levels in the presence of antioxidants. TPEN-induced cell death was also dependent on the redox cycling of copper since the copper chelator neocuproine inhibited DNA damage and reduced pChk1, gamma-H2AX, and ATM protein expression. Cell death by low TPEN concentrations, involved ATM/ATR signaling in all 3 cell lines, since pre-incubation with specific inhibitors of ATM and DNA-PK led to the recovery of cells from TPEN-induced DNA damage.

References: Cancer Biol Ther. 2016 Nov; 17(11):1139-1148; J Vet Med Sci. 2016 Jun 1; 78(5):761-7.