Unknown

Dataset Information

0

Metformin prevents cell tumorigenesis through autophagy-related cell death.


ABSTRACT: Autophagy is a cellular mechanism by which cells degrade intracellular components in lysosomes, maintaining cellular homeostasis. It has been hypothesized that autophagy could have a role in cancer prevention through the elimination of damaged proteins and organelles; this could explain epidemiological evidence showing the chemopreventive properties of the autophagy-inducer metformin. In this study, we analyzed the autophagy-related effect of metformin in both cancer initiation and progression in non-tumorigenic cells. We also analyzed the induction of tumorigenesis in autophagy-deficient cells, and its correlation with the ER stress. Our results showed that metformin induced massive cell death in preneoplastic JB6 Cl 41-5a cells treated with tumor promoter (phorbol) and in NIH/3T3 treated with H2O2. Inhibiting autophagy with wortmannin or ATG7 silencing, the effect of metformin decreased, indicating an autophagy-related cytotoxic activity under stress conditions. We also found an induction of tumorigenesis in ATG7-silenced NIH/3T3 cell clone (3T3-619C3 cells), but not in wild-type and in scrambled transfected cells, and an upregulation of unfolded protein response (UPR) markers in 3T3-619C3 cells treated with H2O2. These findings suggest that autophagic cell death could be considered as a new mechanism by which eliminate damaged cells, representing an attractive strategy to eliminate potential tumorigenic cells.

SUBMITTER: De Santi M 

PROVIDER: S-EPMC6329809 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Metformin prevents cell tumorigenesis through autophagy-related cell death.

De Santi Mauro M   Baldelli Giulia G   Diotallevi Aurora A   Galluzzi Luca L   Schiavano Giuditta Fiorella GF   Brandi Giorgio G  

Scientific reports 20190111 1


Autophagy is a cellular mechanism by which cells degrade intracellular components in lysosomes, maintaining cellular homeostasis. It has been hypothesized that autophagy could have a role in cancer prevention through the elimination of damaged proteins and organelles; this could explain epidemiological evidence showing the chemopreventive properties of the autophagy-inducer metformin. In this study, we analyzed the autophagy-related effect of metformin in both cancer initiation and progression i  ...[more]

Similar Datasets

| S-EPMC3192328 | biostudies-literature
2020-05-09 | GSE131033 | GEO
| S-EPMC3257192 | biostudies-literature
| S-EPMC4496227 | biostudies-literature
| PRJNA542349 | ENA
| S-EPMC3324649 | biostudies-literature
| S-EPMC6567416 | biostudies-literature
| S-EPMC3186904 | biostudies-other
| S-EPMC3957082 | biostudies-other
| S-EPMC2802318 | biostudies-literature