Inhibition of Heme Export and/or Heme Synthesis Potentiates Metformin Anti-Proliferative Effect on Cancer Cell Lines.
ALAS1
FLVCR1
FLVCR1a
cancer
heme
metabolism
metformin
mitochondria
therapy
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
27 Feb 2022
27 Feb 2022
Historique:
received:
03
12
2021
revised:
28
12
2021
accepted:
24
02
2022
entrez:
10
3
2022
pubmed:
11
3
2022
medline:
11
3
2022
Statut:
epublish
Résumé
Cancer is one of the leading causes of mortality worldwide. Beyond standard therapeutic options, whose effectiveness is often reduced by drug resistance, repurposing of the antidiabetic drug metformin appears promising. Heme metabolism plays a pivotal role in the control of metabolic adaptations that sustain cancer cell proliferation. Recently, we demonstrated the existence of a functional axis between the heme synthetic enzyme ALAS1 and the heme exporter FLVCR1a exploited by cancer cells to down-modulate oxidative metabolism. In colorectal cancer cell lines, the inhibition of heme synthesis-export system was associated with reduced proliferation and survival. Here, we aim to assess whether the inhibition of the heme synthesis-export system affects the sensitivity of colorectal cancer cells to metformin. Our data demonstrate that the inhibition of this system, either by blocking heme efflux with a
Identifiants
pubmed: 35267538
pii: cancers14051230
doi: 10.3390/cancers14051230
pmc: PMC8908972
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Italian Association for Cancer Research
ID : 18857
Organisme : Italian Association for Cancer Research
ID : 24922
Organisme : Fondazione CRT
ID : 2018.2260
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