Targeting Mitochondrial Citrate Transport in Breast Cancer Cell Lines
Ali Burak Ozkaya,
Hikmet Hakan Aydin.
Lipogenesis is considered to be a very important aspect of cancer metabolism and targeting de novo lipid
synthesis or related pathways are among novel approaches to treat cancer. Many targets of the pathway including ATPcitrate
lyase (ACLY), acetyl-CoA carboxylase and fatty acid synthase have been evaluated for their potential in cancer
treatment. However the role of citrate transport protein (CTP), another important component of lipogenesis pathway, is
not well known for cancer metabolism and cell survival.
Here we report that while chemical inhibition of CTP reduces cytoplasmic citrate levels and limits breast cancer cell
viability effectively, siRNA based inhibition had little effect on both. We also compared the effects of CTP inhibition
with ACLY and found that the inhibition of ACLY reduced cytoplasmic citrate levels and limited cell viability more effectively than CTP
inhibition. Finally we have demonstrated that neither cell cycle arrest nor autophagy was induced in cells treated with CTP or ACLY
siRNA. Inhibitions triggered apoptosis but only slightly. Growth inhibitory effects do not occur in normal mammary epithelial MCF-10A
Keywords: ATP-citrate lyase, cancer metabolism, citrate transport protein, histone acetylation, SLC25A1.
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