title: Multiple Pharmacological Properties of a Novel Parthenin Analog P16 as Evident by its Cytostatic and Antiangiogenic Potential Against Pancreatic Adenocarcinoma PANC -1 Cells.
abstract: 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.
authors: Akshra
authors: A
authors: Goswami
authors: Bhahwal Ali
authors: BA
authors: Shah
authors: Navneet
authors: N
authors: Batra
authors: Ajay
authors: A
authors: Kumar
authors: Santosh Kumar
authors: SK
authors: Guru
authors: Shashi
authors: S
authors: Bhushan
authors: Fayaz Ahmad
authors: FA
authors: Malik
authors: Department of Biotechnology, SGGS College, Sector-26, Chandigarh 160019, India. amit.molbio@gmail.com.
authors: Amit
authors: A
authors: Joshi
authors: Department of Biotechnology, Panjab University, Chandigarh, 160014, India. jagtar72@gmail.com.
authors: Jagtar
authors: J
authors: Singh
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000473:pathology*; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D012717:Sesquiterpenes; C022097:parthenin