Khasianine Affects the Expression of Sugar-Sensitive Proteins in Pancreatic Cancer Cells, Which Are Altered in Data from the Rat Model and Patients

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with no effective treatment, particularly in the advanced stage. This study explored the antiproliferative activity of khasianine against pancreatic cancer cell lines of human (Suit2007) and rat (ASML) origin. Khasianine was purified from Solanum incanum fruits by silica gel column chromatography and analyzed by LC-MS and NMR spectroscopy. Its effect in pancreatic cancer cells was evaluated by cell proliferation assay, chip array and mass spectrometry. Proteins showing sensitivity to sugars, i.e. sugar-sensitive lactosyl-Sepharose binding proteins (LSBPs), were isolated from Suit2-007 cells by competitive affinity chromatography. The eluted fractions included galactose-, glucose-, rhamnoseand lactose-sensitive LSBPs. The resulting data were analyzed by Chipster, Ingenuity Pathway Analysis (IPA) and GraphPad Prism. Khasianine inhibited proliferation of Suit2-007 and ASML cells with IC50 values of 50 and 54 mu g/mL, respectively. By comparative analysis, khasianine downregulated lactose-sensitive LSBPs the most (126%) and glucose-sensitive LSBPs the least (85%). Rhamnose-sensitive LSBPs overlapped significantly with lactose-sensitive LSBPs and were the most upregulated in data from patients (23%) and a pancreatic cancer rat model (11.5%). From IPA, the Ras homolog family member A (RhoA) emerged as one of the most activated signaling pathways involving rhamnosesensitive LSBPs. Khasianine altered the mRNA expression of sugar-sensitive LSBPs, some of which were modulated in data from patients and the rat model. The antiproliferative effect of khasianine in pancreatic cancer cells and the downregulation of rhamnosesensitive proteins underscore the potential of khasianine in treating pancreatic cancer.