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

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

49 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
Externally published	Yes

Keywords

Drug reprofiling
Mitochondrial respiratory chain
Myeloma
Pyrvinium pamoate
STAT3

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.canlet.2011.12.034

Cite this

@article{32197a4b6e9f4991834ebae28032caeb,

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",

month = jun,

day = "1",

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

language = "English",

volume = "319",

pages = "83--88",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

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

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

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 -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this