<p>Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition</p>

Abstract

These authors contributed equally to this workPurpose: Paeonol, a natural product derived from the root of Cynanchum paniculatum (Bunge) K. Schum and the root of Paeonia suffruticosa Andr. (Ranunculaceae) has attracted extensive attention for its anti-cancer proliferation effect in recent years. The present study examined the role of paeonol in suppressing migration and invasion in pancreatic cancer cells by inhibiting TGF-β1/Smad signaling. Methods: Cell viability was evaluated by MTT and colonial formation assay. Migration and invasion capabilities were examined by cell scratch-wound healing assay and the Boyden chamber invasion assay. Western Blot and qRT-PCR were used to measure the protein and RNA levels of vimentin, E-cadherin, N-cadherin, and TGF-β1/Smad signaling. Results: At non-cytotoxic dose, 100 μΜ and 150 μΜ of paeonol showed significant antimigration and anti-invasion effects on Panc-1 and Capan-1 cells (p<0.01). Paeonol inhibited epithelial-mesenchymal-transition by upregulating E-cadherin, and down regulating N-cadherin and vimentin expressions. Paeonol inhibited TGF-β1/Smad signaling pathway by downregulating TGF-β1, p-Smad2/Smad2 and p-Smad3/Smad3 expressions. Further, TGF-β1 attenuated the anti-migration and anti-invasion capacities of paeonol in Panc-1 and Capan-1 cells. Conclusion: These findings revealed that paeonol could suppress proliferation and inhibit migration and invasion in Panc-1 and Capan-1 cells by inhibiting the TGF-β1/Smad pathway and might be a promising novel anti-pancreatic cancer drug.

Anticancer Activities and Mechanism of Action of Nagilactones, a Group of Terpenoid Lactones Isolated from Podocarpus Species

“…The drug impact on the TGF-β1/Smad signaling pathway is important, not only because it can explain at least partially the anti-fibrotic activity of Nag-D but it can contribute also to the anticancer effects. For example, inhibition of the TGF-β1/Smad pathway has been invoked to explain the anticancer effects of different natural products such as paenol and oridonin [ 41 , 42 ]. Therefore, the recently discovered capacity of Nag-D to regulate the fibroblast-to-myofibroblast transition in atherosclerotic mice deserves further attention because the underlying mechanism is similar to that implicated in the epithelial–mesenchymal transition (EMT) which is known to play a major role to increase motility and invasiveness of cancer cells, and thus to promote cancer metastasis.…”

Paeonol Suppresses Proliferation and Motility of Non-Small-Cell Lung Cancer Cells by Disrupting STAT3/NF-κB Signaling

“…Paeonol (2-hydroxy-4-methoxyacetophenone) has been used as an anti-inflammatory agent ( Lou et al, 2017 ; Zhang L. et al, 2019 ; Zong et al, 2018 ; Al-Taher et al, 2020 ), and also has inhibitory effects on a wide range of cancers including pancreatic, ovarian ( Saahene et al, 2018 ; Gao et al, 2019 ; Cheng et al, 2020 ) ,etc. Recent studies revealed that paeonol could enhance the efficacy of chemotherapeutics, reduce cyclooxygenase-2 (COX-2) and regulate EMT by increasing Human Runt-Related Transcription Factor 3 expression in different types of tumors ( Cai et al, 2014 ; Whittle et al, 2015 ).…”

HCK promotes glioblastoma progression by TGFβ signaling

“…TGFβ and hypoxia have been reported to trigger the process of EMT, suggesting HCK may play an important role in EMT in GBM development [22,23]. EMT, a trans differentiation process converting epithelial cells into motile mesenchymal cells, is involved in the induction of multiple signaling pathways, and leads to cancer progression [24,25]. Previous studies have indicated that EMT is identified as a mechanism resulting in the invasive phenotype of GBM cells [26,27].…”