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/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.
| Original language | English |
|---|---|
| Pages (from-to) | 83-88 |
| Number of pages | 6 |
| Journal | Cancer Letters |
| Volume | 319 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2012 Jun 1 |
| Externally published | Yes |
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Keywords
- Drug reprofiling
- Mitochondrial respiratory chain
- Myeloma
- Pyrvinium pamoate
- STAT3
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3. / Harada, Yasuo; Ishii, Isao; Hatake, Kiyohiko; Kasahara, Tadashi.
In: Cancer Letters, Vol. 319, No. 1, 01.06.2012, p. 83-88.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3
AU - Harada, Yasuo
AU - Ishii, Isao
AU - Hatake, Kiyohiko
AU - Kasahara, Tadashi
PY - 2012/6/1
Y1 - 2012/6/1
N2 - 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.
AB - 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.
KW - Drug reprofiling
KW - Mitochondrial respiratory chain
KW - Myeloma
KW - Pyrvinium pamoate
KW - STAT3
UR - http://www.scopus.com/inward/record.url?scp=84858073770&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858073770&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2011.12.034
DO - 10.1016/j.canlet.2011.12.034
M3 - Article
C2 - 22210382
AN - SCOPUS:84858073770
VL - 319
SP - 83
EP - 88
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -