Grape Seed Proanthocyanidins Inhibit Migration and Invasion of Bladder Cancer Cells by Reversing EMT through Suppression of TGF-β Signaling Pathway.

Bladder cancer (BC) is the most common cancer of the urinary system. Despite advances in diagnosis and therapy, the prognosis is still poor because of recurrence and metastasis. Epithelial-mesenchymal transition (EMT) is considered to play an important role in the invasion and metastasis of BC. Grape seed proanthocyanidins (GSPs) exhibit chemopreventive and chemotherapeutic activities against several types of cancer. However, their effects and underlying mechanisms on the invasive potential of BC remain unclear. In this study, we found that GSPs inhibited migration, invasion, and MMP-2/-9 secretion of both T24 and 5637 bladder cancer cells at noncytotoxic concentrations. We also discovered that 5637 cells were more suitable than T24 cells for the EMT study. Further study showed that GSPs inhibited EMT by reversing the TGF-β-induced morphological change and upregulation of mesenchymal markers N-cadherin, vimentin, and Slug as well as downregulation of epithelial markers E-cadherin and ZO-1 in 5637 cells. GSPs also inhibited TGF-β-induced phosphorylation of Smad2/3, Akt, Erk, and p38 in 5637 cells without affecting the expression of total Smad2/3, Akt, Erk, and p38. Taken together, the results of the present study demonstrate that GSPs effectively inhibit the migration and invasion of BC cells by reversing EMT through suppression of the TGF-β signaling pathway, which indicates that GSPs could be developed as a potential chemopreventive and therapeutic agent against bladder cancer.

Yang N ，Gao J ，Hou R ，Xu X ，Yang N ，Huang S ... -  《-》

Grape seed proanthocyanidins inhibit the invasive potential of head and neck cutaneous squamous cell carcinoma cells by targeting EGFR expression and epithelial-to-mesenchymal transition.

Sun Q ，Prasad R ，Rosenthal E ，Katiyar SK ... -  《BMC Complementary and Alternative Medicine》

Grape seed proanthocyanidins inhibit the invasiveness of human HNSCC cells by targeting EGFR and reversing the epithelial-to-mesenchymal transition.

Sun Q ，Prasad R ，Rosenthal E ，Katiyar SK ... -  《PLoS One》

Grape seed proanthocyanidins inhibit the proliferation, migration and invasion of tongue squamous cell carcinoma cells through suppressing the protein kinase B/nuclear factor-κB signaling pathway.

Yang N ，Gao J ，Cheng X ，Hou C ，Yang Y ，Qiu Y ，Xu M ，Zhang Y ，Huang S ... -  《-》

Grape seed proanthocyanidins inhibit melanoma cell invasiveness by reduction of PGE2 synthesis and reversal of epithelial-to-mesenchymal transition.

Vaid M ，Singh T ，Katiyar SK 《PLoS One》