@article{6dc18ee29f534f53be70234c2e17584e,
title = "Graviola: A novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism",
abstract = "Pancreatic tumors are resistant to conventional chemotherapies. The present study was aimed at evaluating the potential of a novel plant-derived product as a therapeutic agent for pancreatic cancer (PC). The effects of an extract from the tropical tree . Annona Muricata, commonly known as Graviola, was evaluated for cytotoxicity, cell metabolism, cancer-associated protein/gene expression, tumorigenicity, and metastatic properties of PC cells. Our experiments revealed that Graviola induced necrosis of PC cells by inhibiting cellular metabolism. The expression of molecules related to hypoxia and glycolysis in PC cells (i.e. HIF-1α, NF-κB, GLUT1, GLUT4, HKII, and LDHA) were downregulated in the presence of the extract. . In vitro functional assays further confirmed the inhibition of tumorigenic properties of PC cells. Overall, the compounds that are naturally present in a Graviola extract inhibited multiple signaling pathways that regulate metabolism, cell cycle, survival, and metastatic properties in PC cells. Collectively, alterations in these parameters led to a decrease in tumorigenicity and metastasis of orthotopically implanted pancreatic tumors, indicating promising characteristics of the natural product against this lethal disease.",
keywords = "Cancer metabolism, Natural product, Pancreatic cancer, Therapy",
author = "Torres, {Mar{\'i}a P.} and Satyanarayana Rachagani and Vinee Purohit and Poomy Pandey and Suhasini Joshi and Moore, {Erik D.} and Johansson, {Sonny L.} and Singh, {Pankaj K.} and Ganti, {Apar K.} and Batra, {Surinder K.}",
note = "Funding Information: The invaluable technical support from Kavita Mallya is greatly appreciated. We would like to give special thanks to UNMC professors: Dr. Michel Ouellette for kindly providing CD18/HPAF-Luciferase and HPNE cells, Dr. Shilpa Buch for allowing us to use the Luminescence plate reader, Dr. Vimla Band for allowing us to use the microscope to image tumor H&E and IHC sections, and Dr. Steve Caplan for assisting with the analysis of confocal images and providing us the β-Tubulin antibody. We also thank Janice A. Tayor and James R. Talaska of the Confocal Laser Scanning Microscope Core Facility at UNMC, Victoria B. Smith and Megan Michalak of the UNMC Cell Analysis Core Facility, and Ms. Kristi Berger, the Eppley Cancer Center for editing this manuscript. We are also very grateful for the expertise and involvement of Drs. Amarnath Natarajan and Abijah Nyong from the Chemistry department at UNMC in the bioactivity-guided fractionation of the Graviola extract. The authors of this work are supported by Grants from the National Institutes of Health: NIH-NCI Cancer Biology Training Grant UNMC T32CA009479 (MPT), R01 CA78590, U01EDRN CA111294, R01 CA131944, R01 CA133774, R01 CA 138791, P50 SPORE CA127297 and U54 CA160163. AKG is supported by VA Career Development Award. ",
year = "2012",
month = oct,
day = "1",
doi = "10.1016/j.canlet.2012.03.031",
language = "English (US)",
volume = "323",
pages = "29--40",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1",
}