Paeoniflorin prevents hypoxia-induced epithelial–mesenchymal transition in human breast cancer cells

Abstract

Paeoniflorin (PF) is a monoterpene glycoside extracted from the root of Paeonia lactiflora Pall. Previous studies have demonstrated that PF inhibits the growth, invasion, and metastasis of tumors in vivo and in vitro. However, the effect of PF on hypoxia-induced epithelial–mesenchymal transition (EMT) in breast cancer cells remains unknown. Therefore, the objective of this study was to investigate the effect of PF on hypoxia-induced EMT in breast cancer cells, as well as characterize the underlying mechanism. The results presented in this study demonstrate that PF blocks the migration and invasion of breast cancer cells by repressing EMT under hypoxic conditions. PF also significantly attenuated the hypoxia-induced increase in HIF-1α level. Furthermore, PF prevented hypoxia-induced expression of phosphorylated PI3K and Akt in MDA-MB-231 cells. In conclusion, PF prevented hypoxia-induced EMT in breast cancer cells by inhibiting HIF-1α expression via modulation of PI3K/Akt signaling pathway. This finding provides evidence that PF can serve as a therapeutic agent for the treatment of breast cancer.

Paeoniflorin: a monoterpene glycoside from plants of Paeoniaceae family with diverse anticancer activities

“…Recently, methods for treating breast cancer have being improved; however, the clinic effects for patients are not satisfactory; therefore, further investigations on treatment methods of breast cancer are necessary to improve the cure rate. Recent in‐vitro studies indicate that Paeoniflorin in various concentrations inhibits expression of HIF‐1α through regulating pathway PI3K/Akt, thus prevent against epithelial‐to‐mesenchymal transition (EMT) which is induced by hypoxia on breast cancer cell . Another study indicates that Paeoniflorin inhibits proliferation and invasion of human breast cancer cell lines MDA‐MB‐231 and MCF‐7 through inhibiting pathway Notch1 .…”

“…Recent in-vitro studies indicate that Paeoniflorin in various concentrations inhibits expression of HIF-1a through regulating pathway PI3K/Akt, thus prevent against epithelial-to-mesenchymal transition (EMT) which is induced by hypoxia on breast cancer cell. [36] Another study indicates that Paeoniflorin inhibits proliferation and invasion of human breast cancer cell lines MDA-MB-231 and MCF-7 through inhibiting pathway Notch1. [37] In 2018, Zhang et al [38] found that Paeoniflorin in low concentration successfully inhibits proliferation and invasion of human breast cancer cell line MCF-7 through inhibiting pathway Notch1, then proved Paeoniflorin's antitumour effect additionally.…”

“…Paeoniflorin inhibits activity of gastric cancer cell MGC-803 and induces apoptosis, through up-regulating miR-124 and inhibiting pathways of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and signal-activated transcription factors 3 (STAT3) [33] 2.5, 5, 10 lg/ml Gastric cancer fibroblast GCAFs Inhibit metastasis and invasion of GCAFs through targeted inhibition of pathway IL-6-STAT3-MMP [33] Breast cancer 12.5-50 lmol/l Human breast cancer cell lines MDA-MB-231 and MCF-7 PF inhibits expression of HIF-1a through regulating pathway PI3K/Akt, protects against breast cancer cell hypoxia-induced epithelial-to-mesenchymal transition (EMT) [36] Inhibit proliferation and invasion of breast cancer cell through inhibiting pathway Notch-1 [37] 0, 7.5, 15, 30 lmol/l Breast cancer cell line MCF-7 Inhibit proliferation and invasion of breast cancer cell through inhibiting pathway Notch-1 [38] Lung cancer 40 mg/kg per day Lewis lung carcinomabearing mice model Inhibit tumour growth of Lewi lung carcinoma-bearing mice, and inhibit lung metastasis of Lewi lung carcinoma-bearing mice [40] 1, 3, 10, 30, 100 lmol/l; 20, 40 mg/kg…”

Retracted Article: Down-regulation of Rab10 inhibits hypoxia-induced invasion and EMT in thyroid cancer cells by targeting HIF-1α through the PI3K/Akt pathway

“…The EMT process plays an essential role in cancer progression and the hypoxic environment can stimulate this process, [6][7][8]25 so we investigated the effect of Rab10 down-regulation on hypoxiainduced EMT in thyroid cancer cells. As shown in Fig.…”

Herbal medicine for hand–foot syndrome induced by fluoropyrimidines: A systematic review and meta‐analysis

“…Paeoniflorin upregulated apoptosis of MGC‐803 human gastric carcinoma cells and HT29 human colorectal cancer cells (Chen, Lee, et al, ; Parker et al, ; Zheng et al, ). It inhibited proliferation, invasion, and metastasis of MCF‐7/MDA‐MB‐231 human breast cancer cells and human A549 lung cancer cells (Parker et al, ; Zhang, Yuan, Cui, Xiao, & Jiang, ; Zhou, Wang, Song, & Hu, ). The astragalin contained in P. lactiflora induces apoptosis in A375P and SK‐MEL‐2 melanoma cells (You et al, ).…”