Open Access
Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module
Laura Di Magno
1
,
Simona Manni
2
,
Fiorella Di Pastena
2
,
Sonia Coni
2
,
ALBERTO MACONE
3
,
Sara Cairoli
4
,
Manolo Sambucci
5
,
Paola Infante
1
,
Marta Moretti
2
,
Marialaura Petroni
2
,
C. Nicoletti
6
,
CARLO CAPALBO
2
,
E. De Smaele
7
,
Lucia Di Marcotullio
8
,
Giuseppe Giannini
2
,
Luca Battistini
5
,
Bianca Maria Goffredo
4
,
Franca Podo
9
,
Enzo Agostinelli
10
,
Marella Maroder
2
,
Gianluca Canettieri
11
1
8
10
Publication type: Journal Article
Publication date: 2020-02-11
scimago Q1
wos Q1
SJR: 3.796
CiteScore: 12.9
Impact factor: 6.9
ISSN: 22111247, 26391856
PubMed ID:
32049007
General Biochemistry, Genetics and Molecular Biology
Abstract
Summary The antidiabetic drug phenformin displays potent anticancer activity in different tumors, but its mechanism of action remains elusive. Using Shh medulloblastoma as model, we show here that at clinically relevant concentrations, phenformin elicits a significant therapeutic effect through a redox-dependent but complex I-independent mechanism. Phenformin inhibits mitochondrial glycerophosphate dehydrogenase (mGPD), a component of the glycerophosphate shuttle, and causes elevations of intracellular NADH content. Inhibition of mGPD mimics phenformin action and promotes an association between corepressor CtBP2 and Gli1, thereby inhibiting Hh transcriptional output and tumor growth. Because ablation of CtBP2 abrogates the therapeutic effect of phenformin in mice, these data illustrate a biguanide-mediated redox/corepressor interplay, which may represent a relevant target for tumor therapy.
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Metrics
49
Total citations:
49
Citations from 2024:
15
(30.61%)
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GOST
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Di Magno L. et al. Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module // Cell Reports. 2020. Vol. 30. No. 6. p. 1735-1752.e7.
GOST all authors (up to 50)
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Di Magno L., Manni S., Di Pastena F., Coni S., MACONE A., Cairoli S., Sambucci M., Infante P., Moretti M., Petroni M., Nicoletti C., CAPALBO C., De Smaele E., Di Marcotullio L., Giannini G., Battistini L., Goffredo B. M., Podo F., Agostinelli E., Maroder M., Canettieri G. Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module // Cell Reports. 2020. Vol. 30. No. 6. p. 1735-1752.e7.
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RIS
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TY - JOUR
DO - 10.1016/j.celrep.2020.01.024
UR - https://doi.org/10.1016/j.celrep.2020.01.024
TI - Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module
T2 - Cell Reports
AU - Di Magno, Laura
AU - Manni, Simona
AU - Di Pastena, Fiorella
AU - Coni, Sonia
AU - MACONE, ALBERTO
AU - Cairoli, Sara
AU - Sambucci, Manolo
AU - Infante, Paola
AU - Moretti, Marta
AU - Petroni, Marialaura
AU - Nicoletti, C.
AU - CAPALBO, CARLO
AU - De Smaele, E.
AU - Di Marcotullio, Lucia
AU - Giannini, Giuseppe
AU - Battistini, Luca
AU - Goffredo, Bianca Maria
AU - Podo, Franca
AU - Agostinelli, Enzo
AU - Maroder, Marella
AU - Canettieri, Gianluca
PY - 2020
DA - 2020/02/11
PB - Elsevier
SP - 1735-1752.e7
IS - 6
VL - 30
PMID - 32049007
SN - 2211-1247
SN - 2639-1856
ER -
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BibTex (up to 50 authors)
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@article{2020_Di Magno,
author = {Laura Di Magno and Simona Manni and Fiorella Di Pastena and Sonia Coni and ALBERTO MACONE and Sara Cairoli and Manolo Sambucci and Paola Infante and Marta Moretti and Marialaura Petroni and C. Nicoletti and CARLO CAPALBO and E. De Smaele and Lucia Di Marcotullio and Giuseppe Giannini and Luca Battistini and Bianca Maria Goffredo and Franca Podo and Enzo Agostinelli and Marella Maroder and Gianluca Canettieri},
title = {Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module},
journal = {Cell Reports},
year = {2020},
volume = {30},
publisher = {Elsevier},
month = {feb},
url = {https://doi.org/10.1016/j.celrep.2020.01.024},
number = {6},
pages = {1735--1752.e7},
doi = {10.1016/j.celrep.2020.01.024}
}
Cite this
MLA
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Di Magno, Laura, et al. “Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module.” Cell Reports, vol. 30, no. 6, Feb. 2020, pp. 1735-1752.e7. https://doi.org/10.1016/j.celrep.2020.01.024.