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.

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Abstract

  1. Cancer Lett. 2012 Oct 1;323(1):29-40. doi: 10.1016/j.canlet.2012.03.031. Epub
    2012 Apr 1.

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.

Torres MP(1), Rachagani S(2), Purohit V(3), Pandey P(4), Joshi S(2), Moore ED(2),
Johansson SL(5), Singh PK(1), Ganti AK(6), Batra SK(7).

Author information:
(1)Department of Biochemistry and Molecular Biology, Omaha, NE 68198-5870, USA;
Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE
68198-5870, USA.
(2)Department of Biochemistry and Molecular Biology, Omaha, NE 68198-5870, USA.
(3)Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE
68198-5870, USA.
(4)Department of Environmental, Agricultural & Occupational Health, Omaha, NE
68198-5870, USA.
(5)Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE
68198-5870, USA; Department of Pathology and Microbiology, Omaha, NE 68198-5870,
USA.
(6)Department of Internal Medicine VA Nebraska-Western Iowa Health Care System
and University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
(7)Department of Biochemistry and Molecular Biology, Omaha, NE 68198-5870, USA;
Eppley Institute for Research in Cancer and Allied Diseases, Omaha, NE
68198-5870, USA; Department of Pathology and Microbiology, Omaha, NE 68198-5870,
USA. Electronic address: [email protected]

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.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.canlet.2012.03.031
PMCID: PMC3371140
PMID: 22475682 [Indexed for MEDLINE]