Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3.
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/O(2) 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-ρ(0) 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.
Department of Biochemistry, Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
Yasuo
Y
Harada
Isao
I
Ishii
Kiyohiko
K
Hatake
Tadashi
T
Kasahara
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D042967:Electron Transport Complex I / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D011774:Pyrvinium Compounds / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D000970:Antineoplastic Agents; D011774:Pyrvinium Compounds; D050796:STAT3 Transcription Factor; C024631:pyrvinium; D042967:Electron Transport Complex I