Pancreatic ductal adenocarcinoma (PDA) remains one of the deadliest types of
cancers. Median survival rate is very poor with the currently available chemotherapeutical
regimens. Therefore, discovery of new antineoplastic agents against PDA is one of the focused
areas of contemporary research. The present study was undertaken to explore the antitumour activity of a potent parthenin analog P16.
Among PANC-1, Mia PaCa-2 and AsPC-1 pancreatic cancer cells, PANC-1 showed highest sensitivity to P16 with an IC50 value of 3.4
μM. Time dependent cell cycle studies revealed that P16 suppressed the growth of PANC-1 cells by arresting the progression through the
cell cycle in G2/M phase via downregulation of cyclin B1 and cyclin A. However, P16 did not alter the expressions of CDK-1 and
CDC25C in PANC-1 cells. The P16 induced cell cycle arrest, which consequently, led to induction of apoptosis, which was accompanied
by activation of caspase-9 and -3. Interestingly, PANC-1 cells displayed increasing loss of mitochondrial potential, which seemed to be
correlated to the activation of caspase-3. Additionally, P16 was also able to down-regulate the cell migration in PANC-1 cells.
Furthermore, P16 treatment of hypoxic PANC-1 cells strongly suppressed the expression of proangiogenic factors VEGFR-2, HIF1α and
HIF1β. Antiangiogenic ability of P16 was also reflected in the human umbilical vascular endothelial cells (HUVECs), where it
effectively suppressed the migration and inhibited the formation of the tube in a matrigel based assay. Therefore, cytostatic and
antiangiogenic properties of P16 against pancreatic adenocarcinoma cells make it a suitable candidate for further investigation.