Abstract 4128: Anti-angiogenic and anti-metastatic activities of juglone in pancreatic cancer cells

Abstract

Abstract Pancreatic cancer is the fourth leading cause of cancer related deaths in the US. The late diagnosis, early metastasis and poor survival rate make this disease lethal. This current study was designed to examine the effect of juglone, 5 hydroxy-1, 4-naphthoquinone in modulating the angiogenic and metastatic potential of pancreatic cancer cells in vitro, using the MIA Paca-2 human pancreatic cancer cell line. Juglone is a natural quinoid abundantly found abundantly in plants of Juglandacea family. To understand the anti-angiogenic and anti-metastatic properties of juglone, expression of markers related to angiogenesis were measured by Western blot or ELISA and the effect on ability of cancer cells to migrate and invade after treatment was analyzed by transwell invasion and migration assay, wound healing assay, and in vitro tube formation assay in human umbilical vein endothelial cells. The Akt pathway is highly upregulated and is responsible for the regulation of various biological processes in pancreatic cancer cells including proliferation, growth, survival and angiogenesis. Akt activation is also associated with regulation of key angiogenic markers such as, VEGF (Vascular Endothelial Growth Factor) and HIF-1 (Hypoxia Inducible Factor). Upon treatment of pancreatic cancer cells with juglone, reduced expression of serine-phosphorylated Akt expression was observed. Juglone inhibited metastasis of pancreatic cancer cells as indicated by the results of cell migration, invasion and wound healing assay. Juglone treatment also downregulated the levels of VEGF and HIF-1α. Significantly, it was found that juglone inhibited pancreatic cancer cell motility, migratory and invading capabilities. These findings suggest that Akt inhibitors such as juglone possess ability to attenuate the aggressiveness of pancreatic cancer cells and can be used as a novel anti-cancer agent to prevent metastasis of highly invasive pancreatic adenocarcinomas. Citation Format: Namrata Karki, Frank Greenway, William Hansel, Sita Aggarwal, Jack N. Losso. Anti-angiogenic and anti-metastatic activities of juglone in pancreatic cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4128.