Tranexamic Acid (TA) is a clinically used
antifibrinolytic agent that acts as a Lys mimetic to block binding of
Plasminogen with
Plasminogen activators, preventing conversion of
Plasminogen to its proteolytically activated form,
Plasmin. Previous studies suggested that TA may exhibit anticancer activity by blockade of extracellular
Plasmin formation.
Plasmin-mediated cleavage of the CDCP1
protein may increase its oncogenic functions through several downstream pathways. Results presented herein demonstrate that TA blocks
Plasmin-mediated excision of the extracellular domain of the
oncoprotein CDCP1. In vitro studies indicate that TA reduces the viability of a broad array of human and murine
cancer cell lines, and
breast tumor growth studies demonstrate that TA reduces
cancer growth in vivo. Based on the ability of TA to mimic Lys and Arg, we hypothesized that TA may perturb multiple processes that involve Lys/Arg-rich
protein sequences, and that TA may alter intracellular signaling pathways in addition to blocking extracellular
Plasmin production. Indeed, TA-mediated suppression of
tumor cell viability is associated with multiple biochemical actions, including inhibition of
protein synthesis, reduced activating phosphorylation of STAT3 and S6K1, decreased expression of the MYC
oncoprotein, and suppression of Lys acetylation. Further, TA inhibited uptake of Lys and Arg by
cancer cells. These findings suggest that TA or TA analogs may serve as lead compounds and inspire the production of new classes of
anticancer agents that function by mimicking Lys and Arg.