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
| Autor: | Esther A. Guzmán, Jacob D. Johnson, Amy E. Wright, Sarath E. Gunasekera, Patricia Linley |
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| Rok vydání: | 2010 |
| Předmět: |
MAP Kinase Signaling System
Carbazoles Apoptosis Biology Article Metastasis TNF-Related Apoptosis-Inducing Ligand Glycogen Synthase Kinase 3 Cell Movement GSK-3 Cell Line Tumor Pancreatic cancer medicine Humans Pharmacology (medical) Neoplasm Metastasis Extracellular Signal-Regulated MAP Kinases Protein Kinase Inhibitors Cell Proliferation Mitogen-Activated Protein Kinase Kinases Pharmacology Glycogen Synthase Kinase 3 beta Kinase Cell growth Cancer medicine.disease Cell biology Pancreatic Neoplasms Oncology Cancer cell Cancer research Drug Screening Assays Antitumor |
| Zdroj: | Investigational New Drugs. 29:777-785 |
| ISSN: | 1573-0646 0167-6997 |
| DOI: | 10.1007/s10637-010-9422-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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