The natural compound codonolactone attenuates TGF-β1-mediated epithelial-to-mesenchymal transition and motility of breast cancer cells

Abstract

Codonolactone (CLT), a natural product, is the major bioactive component of Atractylodes lancea, and also found in a range of other medical herbs, such as Codonopsis pilosula, Chloranthus henryi Hemsl and Atractylodes macrocephala Koidz. This sesquiterpene lactone has been demonstrated to exhibit a range of activities, including anti-allergic activity, anti-inflammatory, anticancer, gastroprotective and neuroprotective activity. Previously, we found that CLT showed significant anti-metastatic properties in vitro and in vivo. In order to determine whether EMT-involved mechanisms contribute to the anti-metastatic effects of CLT, we checked the anti-EMT properties of CLT and its potential mechanisms. Here it was demonstrated that CLT inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, downregulation of TGF-β signaling was associated with the anti-EMT properties of CLT. Data from western blotting showed that, in breast cancer cells, TGF-β1 stimulated the activation of Runx2, and CLT blocked the activation of Runx2. Finally, to verify whether CLT-induced EMT inhibition leads to suppression of metastatic potential, the effects of CLT on cell invasion and migration were determined. It was found that TGF-β1-induced migration and invasion was significantly blocked by CLT in both MDA-MB-231 and MDA-MB-468 cells. Collectively, our findings demonstrated that CLT inhibited programming of EMT in vitro and in vivo, resulting in inhibition of motility of metastatic breast cancer cells. The inhibitory effect of CLT was due to its ability to inhibit TGF-β signaling and Runx2 phosphorylation.

Fangjihuangqi Decoction inhibits MDA‐MB‐231 cell invasion in vitro and decreases tumor growth and metastasis in triple‐negative breast cancer xenografts tumor zebrafish model

“…Codonolactone is the main bioactive component of Rhizoma Atractylodis macrocephalae . Both in vitro and in vivo studies have reported that codonolactone inhibited EMT and breast cancer metastasis by downregulating TGF‐β signaling pathway and Runx2 phosphorylation . Our experiment results confirmed that FH could prevent tumor metastasis in TNBC xenograft tumor zebrafish and reverse EMT in TGFβ1‐treated MDA‐MB‐231 cells.…”

Parthenolide promotes apoptotic cell death and inhibits the migration and invasion of SW620 cells

“…Antrocin exhibited inhibitory activity on the growth, migration, and invasion of human bladder cancer cells 30. Codonolactone also attenuated transforming growth factor-β1-mediated EMT and motility of breast cancer cells 31. Moreover, it has been reported that costunolide, derived from Saussurea lappa , induces apoptosis and inhibits cell migration and invasion in neuroblastoma cells 32.…”

Mechanisms of TGFβ-Induced Epithelial–Mesenchymal Transition

“…In addition, some compounds enriched from herbs or other natural sources have proven effective in blocking TGFβ-induced EMT, which may explain their potency in reducing the metastatic potential of breast cancer cell models in recipient mice [ 217 ]. One such compound is curcumin, which has been used in the treatment of various tumors and recently was shown to promote epithelial features in thyroid carcinoma cells by counteracting the actions of TGFβ.…”