Tsoong induces apoptosis and inhibits proliferation, migration and invasion of pancreatic ductal adenocarcinoma cells

Abstract

The roots of Codonopsis cordifolioidea (classified as campanulaceae cordifolioidea), locally known as Tsoong, have been used as a tonic food. The major components isolated from Tsoong have been demonstrated to present anti-human immunodeficiency virus-1 activities and cytotoxicity against various tumor cell lines. However, the possible effects of the novel compound isolated from Tsoong, cordifoliketones A, on pancreatic ductal adenocarcinoma (PDAC) cells, are still unknown. In the present study, cordifoliketones A extractions were prepared from Tsoong, and the possible effects on PDAC cell growth, apoptosis, migration and invasion in vitro and in vivo were exlored. The cytotoxicity assay, apoptosis assay, western blotting, migration and invasion assay, and a PDAC cell (AsPC-1, BxPC-3 and PANC-1) xenograft mice model were employed. The results demonstrated that treatment with cordifoliketones A: i) inhibited proliferation and promoted apoptosis of PDAC cells; ii) significantly induced apoptosis and altered expression of apoptosis-associated proteins in a dose-dependent manner; iii) suppressed migration and invasion of PDAC cells in a dose-dependent manner; and iv) restrained the growth of PDAC neoplasm in nude mice. Furthermore, cordifoliketones A demonstrated non-cytotoxic activity in a panel of normal human cells, including hTERT-HPNE, 293, hepatocyte HL-7702 and HL-1 cells. Therefore, these data indicated that cordifoliketones A may be a potential candidate compound for the prevention of PDAC cell proliferation and metastasis, presumably by induction apoptosis and inhibiting viability, invasion and migration of PDAC cells.