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2015 ; 6
(17
): 15652-61
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Metformin-induced energy deficiency leads to the inhibition of lipogenesis in
prostate cancer cells
#MMPMID26002551
Loubière C
; Goiran T
; Laurent K
; Djabari Z
; Tanti JF
; Bost F
Oncotarget
2015[Jun]; 6
(17
): 15652-61
PMID26002551
show ga
The deregulation of lipid metabolism is a hallmark of tumor cells, and elevated
lipogenesis has been reported in prostate cancer. Metformin, a drug commonly
prescribed for type II diabetes, displays antitumor properties. Here, we show
that metformin inhibits lipogenesis in several prostate cancer cell lines. In
LNCaP cells, this effect parallels the decrease of key lipogenic proteins: ACC
(acetyl-CoA carboxylase), FASN (fatty acid synthase) and SREBP1c (sterol
regulatory element binding protein-1c), whereas there is no modification in DU145
and PC3 cells. Despite the relatively high level of lipogenic proteins induced by
the overexpression of a constitutively active form of SREBP1c or treatment with
androgens, metformin is still able to inhibit lipogenesis. Metformin does not
alter the concentration of malonyl-CoA (the fatty acid precursor), and it only
slightly decreases the NADPH levels, which is a co-factor required for
lipogenesis, in LNCaP. Finally, we show that the inhibitory effect of metformin
on lipogenesis is primarily due to a cellular energy deficit. Metformin decreases
ATP in a dose-dependent manner, and this diminution is significantly correlated
with the inhibition of lipogenesis in LNCaP and DU145. Indeed, the effect of
metformin is linked to changes in the ATP content rather than the regulation of
protein expression. Our results describe a new mechanism of action for metformin
on prostate cancer metabolism.