期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 162, 期 -, 页码 107-115出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2020.06.054
关键词
Polygala tenuifolia; Pectin; Pancreatic cancer; Apoptosis; Autophagy
资金
- Key New Drug Creation and Manufacturing Program [2019ZX09735001]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA12020373]
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant carcinomas, which is characterized by apoptosisand autophagy-dependent tumorigenic growth. Autophagy constitutes a stress adaptation that suppresses apoptosis. To explore new leading compound against PDAC, a pectin-like polysaccharide named RP02-1, was purified from roots of Polygala tenuifolia. Bioactivity test showed that RP02-1 might inhibit pancreatic cancer cells growth in vitro and in vivo. RP02-1 could inhibit pancreatic cancer cell (AsPC-1 and BxPC-3) proliferation, migration and colony formation. Mechanism study suggested that RP02-1 induced pancreatic cancer cells apoptosis, which was detected by Bcl-2 down-regulation, Bax up-regulation and conversion from Caspase 3 to Cleaved Caspase 3. Interestingly, autophagy was suppressed by RP02-1 treatment concentration dependently through affenuatingBeclin-1, ATG5 and LC3B expression in BxPC-3 cells. In addition, RP02-1 could inhibit autophagy induced by Pennogenin 3-O-beta-chacotrioside. However, RP02-1 had almost no toxicity both in vitro and in vivo. The above results suggested that RP02-1 might be a potential leading compound for new drug candidate development for human PDAC treatment via inducing apoptosis and against autophagy. (c) 2020 Elsevier B.V. All rights reserved.
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