Abstract 5418: α-Mangostin, a dietary xanthone, inhibits ectopic xenograft growth of pancreatic cancer cells in an athymic nude mice
Authors: Bilal B. Hafeez, Joe W. Fischer, Ala Mustafa, Weixiong Zhong, Ajit K. Verma
Journal: Cancer Research (2012)

Abstract Pancreatic cancer (PC), the most aggressive malignant disease, ranks fourth most leading cause of cancer related death among men and woman in United States. Therefore, it is necessary to intensify our efforts for a better understanding of this disease and for the development of novel therapeutic strategies for its prevention and treatment. One approach to control this malignancy is to slow its progression through the use of natural agents present in the diet consumed by humans. α-Mangostin (MG), a xanthone constituent isolated from the pericarp of Mangosteen fruit (Garcinia mangostana), possesses various health promoting benefits including anti-oxidant, anti-inflammatory, anti-angiogenic and anti-cancer properties. We have previously shown that MG treatment induces apoptosis and inhibits growth of human PC cells via targeting NF-kB, Stat3 and Hedgehog signalings. Here, we determined the anti-tumor potential of MG against human PC in a xenograft mouse model. Highly aggressive human PC ASPC1 cells (2X106) were injected subcutaneously into the flanks of 14 athymic nude mice. Three days post-injection, mice were randomly divided into two groups. One group of mice was administered with MG (6 mg/kg body wt. i.p) in a 0.2 ml of PBS containing 25% polyethylene glycol (PEG) for 7 weeks. Vehicle control group mice were administered with 0.2 ml of PBS containing 25% PEG. Tumor volume of both group animals was measured and their body weight recorded weekly. All the mice of both groups were sacrificed when the tumor size of the control mice reached 1000 mm3. We observed that MG treatment inhibited the growth of ASPC1 cells in a xenograft mouse model as determined by significant (P&amp;lt;0.01) reduction in both the volume and weight of the tumors. Importantly, MG treatment inhibited angiogenesis as determined by the reduced number and size of blood capillaries at tumor sites. Vascular endothelial growth factor receptor (VEGF) is one of the components involved in tumor angiogenesis and metastasis. Immunohistochemistry (I.H.C) results demonstrated that MG treatment significantly reduced the expression of VEGF in xenograft tumors. Also, MG treatment inhibited markers of cell proliferation (ki67 and PCNA) in the xenograft tumor tissues as determined by I.H.C. No sign of toxicity was observed in any of the mice administered with MG as determined by histopathological examination of lungs, liver, kidneys and heart. One mouse from the control group showed metastatic foci of PC cells in the lungs but none of the MG treated animals showed any metastasis into any of the organs. These finding suggest that MG may reduce the metastatic burden of human PC. Taken together these results suggest that MG is a non-toxic dietary agent with anti-tumor potential against human PC. MG could be used as a novel dietary agent for the therapy of human PC. (Support: Department Pilot Project). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5418. doi:1538-7445.AM2012-5418