Lipoic acid decreases breast cancer cell proliferation by inhibiting IGF-1R via furin downregulation.

Published on Jan 28, 2020in British Journal of Cancer5.416
· DOI :10.1038/s41416-020-0729-6
Diana Farhat1
Estimated H-index: 1
Sophie Léon2
Estimated H-index: 2
+ 5 AuthorsHubert Lincet11
Estimated H-index: 11
Breast cancer is the second most common cancer in the world. Despite advances in therapies, the mechanisms of resistance remain the underlying cause of morbidity and mortality. Lipoic acid (LA) is an antioxidant and essential cofactor in oxidative metabolism. Its potential therapeutic effects have been well documented, but its mechanisms of action (MOA) are not fully understood. The aim of this study is to validate the inhibitory LA effect on the proliferation of various breast cancer cell lines and to investigate the MOA that may be involved in this process. We tested LA effects by ex vivo studies on fresh human mammary tumour samples. We demonstrate that LA inhibits the proliferation and Akt and ERK signalling pathways of several breast cancer cells. While searching for upstream dysregulations, we discovered the loss of expression of IGF-1R upon exposure to LA. This decrease is due to the downregulation of the convertase, furin, which is implicated in the maturation of IGF-1R. Moreover, ex vivo studies on human tumour samples showed that LA significantly decreases the expression of the proliferation marker Ki67. LA exerts its anti-proliferative effect by inhibiting the maturation of IGF-1R via the downregulation of furin.
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