Abstract
Baicalein, a flavone ingredient of Scutellaria baicalensis Georgi, is a promising anti-cancer agent. However, its potential anti-pancreatic cancer effects and the underlying mechanisms are still unclear. In this study, we showed that Baicalein not only induced apoptosis, but also suppressed proliferation, migration and invasion of two pancreatic cancer cell lines BxPC-3 and PANC-1 in a dose- and time-dependent manner. Notably, Baicalein exhibited low toxicity to normal human liver or kidney cells. We further discovered that Baicalein suppressed BxPC-3 and PANC-1 cell proliferation and invasion through targeting the expression of NEDD9, a Cas scaffolding protein, to decrease Akt and ERK activities. Especially, Baicalein decreased Akt phosphorylation at T-308 via lowering NEDD9-dependent PDK1 expression. Overexpression of NEDD9 effectively rescued proliferation and invasion of BxPC-3 and PANC-1 cells dampened by Baicalein. Taken together, our findings suggest that Baicalein is a potent remedy applied to pancreatic cancer treatment in the future.
Highlights
Pancreatic cancer, especially the pancreatic ductal adenocarcinoma, is a devastating disease with high mortality and has a 5-year survival rate less than 5%
As the activation of PI3K/Akt and/or MEK/ERK is important for the invasion of human pancreatic cancer cells [36, 37], we investigated the effects of Baicalein on these two signaling pathways in BxPC-3 and PANC1 cells
We demonstrated that Baicalein could effectively inhibit the proliferation, migration, and invasion of BxPC-3 and PANC-1 cells, as well as cause a massive cell death, which was achieved through suppressing the PI3K/Akt and MEK/ERK signaling activation in a dose- and time-dependent manner
Summary
Pancreatic cancer, especially the pancreatic ductal adenocarcinoma, is a devastating disease with high mortality and has a 5-year survival rate less than 5%. Once diagnosed, the cancer has already reached the advanced stages characterized by remarkable aggression and malignancy. Distant metastasis accounts for 90% death caused by pancreatic cancer, as revealed by clinical inspections [2, 3]. The effectiveness of surgical resection therapy for pancreatic cancer is greatly reduced. Chemotherapy and radiation therapy are the supplementary schemes; pancreatic cancer cells are highly resistant to the traditional chemotherapeutic agents, such as Gemcitabine [4]. There is still lack of potent and low-toxic medication available for the treatment of pancreatic cancer patients
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