Diosgenin inhibits the epithelial‑mesenchymal transition initiation in osteosarcoma cells via the p38MAPK signaling pathway

Abstract

Diosgenin is an important basic raw material for the production of steroid hormone drugs. It can be isolated and purified from a variety of traditional Chinese medicines or plants. Modern molecular biological studies have shown that diosgenin inhibits various tumor cells migration and invasion ability to varying degrees in vitro and in vivo. The aim of the present study was to observe the inhibitory effects of diosgenin on the invasive and metastatic capabilities of osteosarcoma cells and to determine the association between the effects of diosgenin on the epithelial-mesenchymal transition (EMT). Wound healing and Transwell assays were used to observe the inhibitory effects of diosgenin on the invasion and migration of two osteosarcoma cell lines. Immunofluorescence was used to observe changes in transforming growth factor β1 (TGF-β1) protein expression levels in the osteosarcoma cells following drug administration. EMT-associated proteins, including TGFβ1, E-cadherin and vimentin were detected by western blotting, which demonstrated that the drug may inhibit the initiation of EMT in osteosarcoma cells. Western blot analysis of the expression of all the proteins in the mitogen-activated protein kinase (MAPK) pathway demonstrated that the drug inhibited the MAPK signaling pathway. The primary mechanism of action of diosgenin was the inhibition of the phosphorylated p38 (pP38) protein. Through a combination of inhibitors of the p38MAPK signaling pathway and detection of the downstream EMT marker protein E-cadherin by quantitative PCR, pP38 was confirmed to be a target of diosgenin in the inhibition of EMT in the osteosarcoma cells via the MAPK molecular signaling pathway. Diosgenin may exhibit utility as an auxiliary drug for the clinical reduction of metastasis in patients with osteosarcoma.

Down-regulation of PRR11 affects the proliferation, migration and invasion of osteosarcoma by inhibiting the Wnt/β-catenin pathway

“…Wnt signaling pathway is a key signal transduction pathway that induces EMT in epithelial tissues [25,26]. Recent studies by Liu et al confirmed that EMT activation can increase the invasion and metastasis ability of osteosarcoma cells, and promote the progression of osteosarcoma [27,28].…”

Melatonin suppresses epithelial‑to‑mesenchymal transition in the MG‑63 cell line

“…it is generally believed that the eMT phenomenon only occurs in epithelial-derived cells. However, recent studies have shown that certain mesenchymal cells can also alter eMT-related protein and enhance the metastasis process (21,22). osteosarcoma (oa) is the most common bone malignant tumor of mesenchymal origin.…”

Anticancer Activity of Diosgenin and Its Molecular Mechanism

“…(47,66,67) Osteosarcoma is a kind of osteogenic malignant tumor, which has a high incidence in primary malignant bone tumors. (68) Diosgenin could inhibit the invasion and migration of osteosarcoma cells MG63 and U2OS, the proliferation of human osteosarcoma cell 1547, as well as osteosarcoma cell S180, and it could block the cell cycle in G 1 phase and induce apoptosis. (59,68,69)…”

“…(68) Diosgenin could inhibit the invasion and migration of osteosarcoma cells MG63 and U2OS, the proliferation of human osteosarcoma cell 1547, as well as osteosarcoma cell S180, and it could block the cell cycle in G 1 phase and induce apoptosis. (59,68,69)…”

“…(70) Diosgenin may regulate the proliferation, apoptosis, migration and invasion of esophageal, colon cancer and osteosarcoma cells through inhibiting the initiation of epithelial-mesenchymal transition (EMT) and then inhibiting p38-MAPK signal pathway with EMT-related proteins such as transforming growth factor β1, E-cadherin and vimentin, and induce apoptosis of A549 cells via related MAPK signal pathway proteins caspase-8, -9 and -3. (68,71) Noticeably, the anti-tumor effect of diosgenin may also be carried out through multiple pathways at a same time. Diosgenin could inhibit the phosphorylation of NF-κB/p65, IKK-β, Akt, ERK, and JNK, which indicated Bcl-xL and Survivinm RNA.…”