Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3

Yasuo Harada; Isao Ishii; Kiyohiko Hatake; Tadashi Kasahara

doi:10.1016/j.canlet.2011.12.034

Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3

Yasuo Harada, Isao Ishii, Kiyohiko Hatake, Tadashi Kasahara

School of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

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	https://doi.org/10.1016/j.canlet.2011.12.034
Publication status	Published - 2012 Jun 1

Keywords

Drug reprofiling
Mitochondrial respiratory chain
Myeloma
Pyrvinium pamoate
STAT3

ASJC Scopus subject areas

Oncology
Cancer Research

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title = "Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3",

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.",

keywords = "Drug reprofiling, Mitochondrial respiratory chain, Myeloma, Pyrvinium pamoate, STAT3",

author = "Yasuo Harada and Isao Ishii and Kiyohiko Hatake and Tadashi Kasahara",

note = "Funding Information: This work was supported in parts by Grants-in-Aid for Scientific Research 22590292 (I.I.) and 21590072 (T.K.), and Innovative Areas 23117716 (I.I.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.",

year = "2012",

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doi = "10.1016/j.canlet.2011.12.034",

language = "English",

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AU - Harada, Yasuo

AU - Ishii, Isao

AU - Hatake, Kiyohiko

AU - Kasahara, Tadashi

N1 - Funding Information: This work was supported in parts by Grants-in-Aid for Scientific Research 22590292 (I.I.) and 21590072 (T.K.), and Innovative Areas 23117716 (I.I.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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

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Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT3

Abstract

Keywords

ASJC Scopus subject areas

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