Emerging studies have shown that
nigericin, an H+, K+ and Pb2+
ionophore, has exhibited a promising anti-
cancer activity in various
cancers. However, its anti-
cancer mechanisms have not been fully elucidated. In this review, the recent progresses on the use of
nigericin in human
cancers have been summarized. By exchanging H+ and K+ across cell membranes,
nigericin shows promising anti-
cancer activities in in vitro and in vivo as a single agent or in combination with other anti-
cancer drugs through decreasing intracellular pH (pHi). The underlying mechanisms of
nigericin also include the inactivation of Wnt/β-
catenin signals, blockade of
Androgen Receptor (AR) signaling, and activation of Stress-Activated
Protein Kinase/c-
Jun N-terminal Kinase (SAPK/JNK) signaling pathways. In many
cancers,
nigericin is proved to specifically target putative Cancer Stem Cells (CSCs), and its synergistic effects on
photodynamic therapy are also reported. Other mechanisms of
nigericin including influencing the mitochondrial membrane potentials, inducing an increase in drug accumulation and autophagy, controlling
insulin accumulation in nuclei, and increasing the cytotoxic activity of
liposome-entrapped drugs, are also discussed. Notably, the potential adverse effects such as teratogenic effects,
insulin resistance and eryptosis shall not be ignored. Taken together, these reports suggest that treatment of
cancer cells with
nigericin may offer a novel therapeutic strategy and future potential of translation to clinics.