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 (Suit2-007) 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-,
rhamnose- and
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 μg/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
rhamnose-sensitive 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
rhamnose-sensitive
proteins underscore the potential of
khasianine in treating
pancreatic cancer.