Abstract
Pyrvinium pamoate (PP), a classical anthelminthic, potently inhibited proliferation and STAT3 Tyr705 phosphorylation of human myeloma (U266B1 and PCM6)/erythroleukemia (HEL 92.1.7) cells. PCM6 cell proliferation was markedly impaired by STAT3 siRNA knockdown. PP inhibited ATP production/O2 consumption in those three cells and mitochondrial respiratory complex (I+III, but not II+III) activity in mouse kidney mitochondrial fractions. PP inhibition of ATP production, STAT3 Tyr705 phosphorylation, and proliferation was absent in mitochondrial DNA-deficient HEL 92.1.7-ρ0 cells. Moreover, PP acted synergistically with dexamethasone to inhibit PCM6 cell proliferation. In conclusion, we identified PP as a potential anticancer drug directed against mitochondrial respiratory complex I/STAT3.
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