Cyanidin-3-glucoside induces mesenchymal to epithelial transition via activating Sirt1 expression in triple negative breast cancer cells.

Abstract:

:Triple-negative breast cancer (TNBC) is a heterogeneous group of breast cancer with one common feature: distinctly metastatic nature with higher rate of relapse and shorter survival compared with other subtypes of breast cancer. The epithelial to mesenchymal transition (EMT) is highly associated with cancer metastasis. Cyanidin-3-glucoside (C3G), the most abundant anthocyanin pigment enriched in fresh fruits and vegetables, showed ideal anti-oxidant property. C3G could also inhibit certain malignant behaviors of cancer cells, however, whether repression of EMT was involved in its anti-cancer especially TNBC effect remains unknown. Herein, we report that C3G decreases the migratory and invasive nature of TNBC lines MDA-MB-231 and BT-549. Mechanistically, C3G induces reversion of EMT characterized by phenotype modulation with increased epithelial marker E-ca and ZO-1, decreased mesenchymal marker Vimentin, N-ca and EMT-associated transcription factors Snail1, Snail2. NF-κB is pivotal for EMT and Sirt1 is a NF-κB inhibitor. We show that NF-κB is attenuated and Sirt1 is induced by C3G in TNBC, respectively. And later evidence demonstrates that abrogation of Sirt1 with small interfering RNA transfection abolished NF-κB inhibition and EMT reversion by C3G. Subsequently, we show that microRNA-138(miR-138) represses Sirt1 via mRNA translation inhibition and is inhibited by C3G. Moreover, miR-138 repression is involved in Sirt1 re-activation and migratory and invasive inhibition of TNBC by C3G. Taken together, we supplied more evidence to the anti-breast cancer mechanisms of C3G.

journal_name

Biochimie

journal_title

Biochimie

authors

Liang L,Liu X,He J,Shao Y,Liu J,Wang Z,Xia L,Han T,Wu P

doi

10.1016/j.biochi.2019.03.004

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

107-115

eissn

0300-9084

issn

1638-6183

pii

S0300-9084(19)30071-9

journal_volume

162

pub_type

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