Escin inhibits angiogenesis by suppressing interleukin-8 and vascular endothelial growth factor production by blocking nuclear factor-κB activation in pancreatic cancer cell lines

Abstract

Pancreatic cancer (PaCa) is one of the most aggres- sive types of cancer. Thus, the development of new and more effective therapies is urgently required. Escin, a pentacyclic triterpenoid from the horse chestnut, has been reported to exhibit antitumor potential by reducing cell proliferation and blocking the nuclear factor-κB (NF-κB) signaling pathway in several types of cancer. Our previous study reported that NF-κB enhanced the secretion of interleukin (IL)-8 and vascular endo- thelial growth factor (VEGF), thereby inducing angiogenesis in PaCa cell lines. In the present study, it was examined whether escin inhibited angiogenesis by blocking NF-κB activation in PaCa. It was initially confirmed that escin, at concentrations >10 µM, significantly inhibited the proliferation of several PaCa cell lines. Next, using immunocytochemical staining, it was found that escin inhibited the nuclear translocation of NF-κB. Furthermore, ELISA confirmed that NF-κB activity in the escin-treated PaCa cells was significantly inhibited and reverse transcription-quantitative PCR showed that the mRNA expression levels of tumor necrosis factor-α-induced IL-8 and VEGF were significantly suppressed following escin treatment in the PaCa cell lines. ELISA also showed that escin decreased the secretion of IL-8 and VEGF from the PaCa cells. Furthermore, tube formation in immortalized human endothelial cells was inhibited following incubation with the supernatants from escin-treated PaCa cells. These results indicated that escin inhibited angiogenesis by reducing the secretion of IL-8 and VEGF by blocking NF-κB activity in PaCa. In conclusion, escin could be used as a novel molecular therapy for PaCa.