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Investigational New Drugs
Published in: Investigational New Drugs 5/2011

01-10-2011 | PRECLINICAL STUDIES

A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis

Authors: Esther A. Guzmán, Jacob D. Johnson, Patricia A. Linley, Sarath E. Gunasekera, Amy E. Wright

Published in: Investigational New Drugs | Issue 5/2011

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Abstract

Purpose: Pancreatic cancer is the fourth leading cause of cancer death in the United States, and new drugs to treat the disease are needed. Pancreatic cancer cells are highly metastatic and exhibit resistance to apoptosis. Small molecules that can restore sensitivity to apoptosis or reduce metastasis would have therapeutic potential against this disease. Manzamine A is an alkaloid isolated from marine sponges that was suspected to have inhibitory activity against the mitogen activated kinase kinase (MEK). Because of this, the effects of Manzamine A were studied in pancreatic cancer cells. Methods: AsPC-1 cells were treated for 48 h in the presence of various concentrations of Manzamine A and their phenotype, cytotoxicity, cell invasion and susceptibility to apoptosis were observed. Results: Manzamine A decreased single cell formation, abrogated cell migration and restored the susceptibility of the cells to TRAIL-induced apoptosis in AsPC-1 cells. Its mechanism of action remains unknown, as manzamine A does not inhibit MEK. Conclusions: Manzamine A appears to have a formerly unrecognized activity in blocking tumor cell invasion as well as in restoring cancer cell susceptibility to apoptosis in vitro and therefore has the potential to be used as an adjuvant to existing cancer therapies.
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Metadata
Title
A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis
Authors
Esther A. Guzmán
Jacob D. Johnson
Patricia A. Linley
Sarath E. Gunasekera
Amy E. Wright
Publication date
01-10-2011
Publisher
Springer US
Published in
Investigational New Drugs / Issue 5/2011
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-010-9422-6

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