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Sauchinone inhibits the proliferation, migration and invasion of breast cancer cells by suppressing Akt-CREB-MMP13 signaling pathway.

ABSTRACT: Sauchinone, a lignan isolated from Saururus chinenesis, is known to exhibit anti-inflammatory and anti-oxidant effects. Recently, sauchinone has been reported to inhibit the growth of various cancer cells, but its effects on breast cancer cells remain poorly understood. In the present study, we investigated the effects of sauchinone on the growth of breast cancer cells along with the underlying molecular mechanisms. Our results show that sauchinone treatment markedly inhibited the proliferation, migration, and invasion of breast cancer cells. Sauchinone reduced the phosphorylation of Akt, ERK, and CREB increased by transforming growth factor-β (TGF-β). In particular, sauchinone treatment suppressed the expression of matrix metalloproteinase (MMP)-13 (MMP13) by regulating the Akt-CREB signaling pathway. Sauchinone was less effective in inhibiting cell migration in Mmp13-knockdown cells than in control cells, suggesting that MMP13 may be a novel target for sauchinone. Our study suggests that sauchinone inhibits the growth of breast cancer cells by attenuating the Akt-CREB-MMP13 pathway. In addition, the targeted inhibition of MMP13 by sauchinone represents a promising approach for the treatment of breast cancer.

SUBMITTER: Kim NH

PROVIDER: S-EPMC8561391 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Sauchinone inhibits the proliferation, migration and invasion of breast cancer cells by suppressing Akt-CREB-MMP13 signaling pathway.

Kim Na Hui NH Sung Nam Ji NJ Shin Seokwon S Ryu Deok-Seon DS Youn Hyung-Sun HS Park Sin-Aye SA

Bioscience reports 20211001 10

Sauchinone, a lignan isolated from Saururus chinenesis, is known to exhibit anti-inflammatory and anti-oxidant effects. Recently, sauchinone has been reported to inhibit the growth of various cancer cells, but its effects on breast cancer cells remain poorly understood. In the present study, we investigated the effects of sauchinone on the growth of breast cancer cells along with the underlying molecular mechanisms. Our results show that sauchinone treatment markedly inhibited the proliferation, ...[more]

PMID: 34643237

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Project description:The long non‑coding (lnc)RNA named tissue differentiation inducing non‑protein coding RNA (TINCR) is a tumor marker that has not been studied in breast cancer. The present study aimed to investigate the TINCR‑targeting micro (mi)RNAs and the regulatory mechanisms of TINCR in breast cancer. Following prediction by TargetScan and confirmation by dual‑luciferase reporter assay, TINCR was demonstrated to be a target gene for miR‑589‑3p. The expression of TINCR and miR‑589‑3p in breast cancer and adjacent tissues was detected by reverse transcription‑quantitative (RT‑q)PCR, and the correlation between TINCR and miR‑589‑3p expression was determined by using Spearman correlation analysis. The 5‑years survival was analyzed in patients with breast cancer according to TINCR expression (high or low). The effects of TINCR and miR‑589‑3p on the proliferation, apoptosis, migratory and invasive abilities of some breast cancer cell lines were detected by MTT assay, flow cytometry, wound healing assay and Transwell assay. The target gene of miR‑589‑3p was predicted and verified by TargetScan and dual‑luciferase reporter assay, and the mechanism of miR‑589‑3p involvement in breast cancer cells was explored by overexpression or downregulation of miR‑589‑3p in breast cancer cells. RT‑qPCR and western blotting were used to determine the expression of the insulin‑like growth factor 1 receptor (IGF1R)/AKT pathway‑related genes. The results demonstrated that TINCR expression level was negatively correlated with miR‑589‑3p expression level in breast cancer tissues and that patients with high expression of TINCR presented with lower survival rates. In addition, TINCR overexpression in cancer cells inhibited miR‑589‑3p expression, and cell transfection with miR‑589‑3p mimic partially reversed the effect of TINCR overexpression on the promotion of cancer cell proliferation, migration and invasion, and on the inhibition of cancer cell apoptosis. Furthermore, IGF1R, which is a target gene of miR‑589‑3p, increased cancer cell proliferation, migration and invasion and inhibited cancer cell apoptosis; however, these effects were partially reversed by miR‑589‑3p mimic. Furthermore, the results demonstrated that miR‑589‑3p mimic could downregulate the protein expression of IGF1R and p‑AKT. In addition, TINCR overexpression downregulated miR‑589‑3p expression level. miR‑589‑3p partially reversed the effects of TINCR overexpression on cancer cell proliferation, migration and invasion, and inhibited cancer cell apoptosis by inhibiting the IGF1R‑Akt pathway. The results from the present study demonstrated that TINCR may sponge miR‑589‑3p in order to inhibit IGF1R‑Akt pathway activation in breast cancer cells, promoting therefore cancer cell proliferation, migration and invasion.

Dataset Information

Sauchinone inhibits the proliferation, migration and invasion of breast cancer cells by suppressing Akt-CREB-MMP13 signaling pathway.

Publications

Sauchinone inhibits the proliferation, migration and invasion of breast cancer cells by suppressing Akt-CREB-MMP13 signaling pathway.

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