Abstract
Abstract BACKGROUND: Pancreatic cancer is a devastating disease with a dismal survival rate of less than 7%. This is due to its late diagnosis and aggressive, metastatic disease. Currently treatment typically consists of surgery and/or treatment with gemcitabine; gemcitabine/nab-paclitaxel or FOLFIRINOX - all chemotherapeutic agents that have natural product-derived components that only prolong survival by 5-6 months at best. As traditional Vietnamese medicinal plants have been used to treat a number of diseases for several thousands of years, there is great potential to investigate their importance as sources of novel therapeutic agents for pancreatic cancer. METHODS: Pancreatic cancer cell lines (BxPC3, MiaPaCa2 and CFPAC1) and the normal pancreatic ductal epithelial (HPDE) cell line were treated with pure compounds isolated from the Vietnamese plants Croton tonkinensis and Salacia cochinchinensis and the effects on cell viability (CCK-8 assay) and apoptosis (caspase-3/-7 activation assay) were assessed to determine their anti-cancer capacity. RESULTS: Treatment of pancreatic cancer cell lines with Pristimerin (from Salacia cochinchinensis) and CT1 (from Croton tonkinensis) resulted in significant dose-dependent growth inhibition. Pancreatic cancer cell lines showed significantly greater sensitivity to Pristimerin treatment after 24 and 72hrs, with a 1.7 – 2.3 fold lower IC50 value in MiaPaCa2 pancreatic cancer cells compared to normal HPDE cells, respectively (24hrs: 48 vs. 111nM; 72hrs: 63.85 vs. 111nM). Significant cytotoxicity was also seen in other pancreatic cancer cell lines (BxPC3 103 - 210nM; CFPAC1 77nM). Treatment with CT1 also resulted in significant dose-dependent cytotoxicity with an IC50 value that was 1.5 – 1.8 fold lower in MiaPaCa2 cells compared to normal HPDE cells, respectively (24hrs: 116 vs. 177nM; 72hrs: 46.5 vs. 84.5nM). Treatment of BxPC3 and CFPAC1 cells with CT1 also led to significant cytotoxicity with IC50 values of 300nM and 170nM, respectively. Moreover, treatment with Pristimerin and CT1 at concentrations of 625nM and 1μM induced caspase-dependent apoptosis of MiaPaCa2 and HPDE cells after 22hrs of treatment. CONCLUSIONS: Pure compounds from Vietnamese medicinal plants show significant pancreatic cancer growth inhibition and induce apoptosis in vitro at concentrations that have minimal effect on normal pancreatic cells and therefore show promise as novel anti-pancreatic cancer therapies. Note: This abstract was not presented at the meeting. Citation Format: Danielle Bond, Phuong Thien Thuong, Do Thi Ha, Nguyen Minh Khoi, Judith Weidenhofer, Christopher J. Scarlett. Vietnamese medicinal plant compounds show potent anti-pancreatic cancer activity in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2175. doi:10.1158/1538-7445.AM2017-2175
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