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.
Submitted by María del Pilar Torres-González on
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. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Torres, MP, Rachagani, S, Purohit, V, Pandey, P, Joshi, S, Moore, ED, Johansson, SL, Singh, PK, Ganti, AK, Batra, SK |
Journal | Cancer Lett |
Volume | 323 |
Issue | 1 |
Pagination | 29-40 |
Date Published | 2012 Oct 1 |
ISSN | 1872-7980 |
Keywords | Animals, Annona, Antineoplastic Agents, Blotting, Western, Cell Line, Tumor, Cell Movement, Female, Humans, Mice, Mice, Nude, Microscopy, Confocal, Necrosis, Neoplasms, Experimental, Pancreatic Neoplasms, Phytotherapy, Plant Extracts, Real-Time Polymerase Chain Reaction, Signal Transduction, Xenograft Model Antitumor Assays |
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. |
DOI | 10.1016/j.canlet.2012.03.031 |
Alternate Journal | Cancer Lett. |
PubMed ID | 22475682 |
PubMed Central ID | PMC3371140 |
Grant List | CA111294 / CA / NCI NIH HHS / United States P50 CA127297 / CA / NCI NIH HHS / United States R01 CA078590 / CA / NCI NIH HHS / United States R01 CA131944 / CA / NCI NIH HHS / United States R01 CA131944 / CA / NCI NIH HHS / United States R01 CA133774 / CA / NCI NIH HHS / United States R01 CA133774 / CA / NCI NIH HHS / United States R01 CA138791 / CA / NCI NIH HHS / United States R01 CA138791 / CA / NCI NIH HHS / United States R01 CA78590 / CA / NCI NIH HHS / United States T32CA009479 / CA / NCI NIH HHS / United States U54 CA160163 / CA / NCI NIH HHS / United States |