Review of the Apoptosis Pathways in Pancreatic Cancer and the Anti‐apoptotic Effects of the Novel Sea Cucumber Compound, Frondoside A
Pancreatic cancer cells are resistant to the growth‐inhibitory and apoptosis‐inducing effects of conventional chemotherapeutic agents. There are multiple genetic and epigenetic events during the process of carcinogenesis that enable the cancer cells to avoid normal growth constraints and apoptosis....
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crwiley:10.1196/annals.1414.025 2024-09-15T18:03:24+00:00 Review of the Apoptosis Pathways in Pancreatic Cancer and the Anti‐apoptotic Effects of the Novel Sea Cucumber Compound, Frondoside A Li, X. Roginsky, A. B. Ding, X.‐Z. Woodward, C. Collin, P. Newman, R. A. Bell, Jr, R. H. Adrian, T. E. 2008 http://dx.doi.org/10.1196/annals.1414.025 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1196%2Fannals.1414.025 https://nyaspubs.onlinelibrary.wiley.com/doi/pdf/10.1196/annals.1414.025 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Annals of the New York Academy of Sciences volume 1138, issue 1, page 181-198 ISSN 0077-8923 1749-6632 journal-article 2008 crwiley https://doi.org/10.1196/annals.1414.025 2024-08-27T04:28:19Z Pancreatic cancer cells are resistant to the growth‐inhibitory and apoptosis‐inducing effects of conventional chemotherapeutic agents. There are multiple genetic and epigenetic events during the process of carcinogenesis that enable the cancer cells to avoid normal growth constraints and apoptosis. Investigation of the mechanisms involved has led to multiple strategies that encourage cell death and apoptosis to occur. The pathways involved are summarized in this review, together with some recently developed strategies to promote cell death in this cancer and with a particular focus on the frondoside A, a novel triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria frondosa . Frondoside A inhibited proliferation of AsPC‐1 human pancreatic cancer cells in a concentration‐ and time‐dependent manner, as measured by 3 H‐thymidine incorporation and cell counting. In concert with inhibition of cell growth, frondoside A induced significant morphological changes consistent with apoptosis. Propidium iodide DNA staining showed an increase of sub‐G0/G1 cell population of apoptotic cells induced by frondoside A. Frondoside A–induced apoptosis was confirmed by annexin V binding and TUNEL assay. Furthermore, western blotting showed a decrease in expression of Bcl‐2 and Mcl‐1, an increase in Bax expression, activation of caspases 3, 7, and 9, and an increase in the expression of the cyclin‐dependent kinase inhibitor, p21. These findings show that frondoside A induced apoptosis in human pancreatic cancer cells through the mitochondrial pathway and activation of the caspase cascade. Finally, a very low concentration of frondoside A (10 μg/kg/day) inhibited growth of AsPC‐1 xenografts in athymic mice. In conclusion, new chemotherapeutic agents are desperately needed for pancreatic cancer because of the poor responsiveness to currently available treatment options. Frondoside A has potent growth inhibitory effects on human pancreatic cancer cells, and the inhibition of proliferation is accompanied by marked ... Article in Journal/Newspaper Cucumaria frondosa Wiley Online Library Annals of the New York Academy of Sciences 1138 1 181 198 |
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Open Polar |
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Wiley Online Library |
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crwiley |
language |
English |
description |
Pancreatic cancer cells are resistant to the growth‐inhibitory and apoptosis‐inducing effects of conventional chemotherapeutic agents. There are multiple genetic and epigenetic events during the process of carcinogenesis that enable the cancer cells to avoid normal growth constraints and apoptosis. Investigation of the mechanisms involved has led to multiple strategies that encourage cell death and apoptosis to occur. The pathways involved are summarized in this review, together with some recently developed strategies to promote cell death in this cancer and with a particular focus on the frondoside A, a novel triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria frondosa . Frondoside A inhibited proliferation of AsPC‐1 human pancreatic cancer cells in a concentration‐ and time‐dependent manner, as measured by 3 H‐thymidine incorporation and cell counting. In concert with inhibition of cell growth, frondoside A induced significant morphological changes consistent with apoptosis. Propidium iodide DNA staining showed an increase of sub‐G0/G1 cell population of apoptotic cells induced by frondoside A. Frondoside A–induced apoptosis was confirmed by annexin V binding and TUNEL assay. Furthermore, western blotting showed a decrease in expression of Bcl‐2 and Mcl‐1, an increase in Bax expression, activation of caspases 3, 7, and 9, and an increase in the expression of the cyclin‐dependent kinase inhibitor, p21. These findings show that frondoside A induced apoptosis in human pancreatic cancer cells through the mitochondrial pathway and activation of the caspase cascade. Finally, a very low concentration of frondoside A (10 μg/kg/day) inhibited growth of AsPC‐1 xenografts in athymic mice. In conclusion, new chemotherapeutic agents are desperately needed for pancreatic cancer because of the poor responsiveness to currently available treatment options. Frondoside A has potent growth inhibitory effects on human pancreatic cancer cells, and the inhibition of proliferation is accompanied by marked ... |
format |
Article in Journal/Newspaper |
author |
Li, X. Roginsky, A. B. Ding, X.‐Z. Woodward, C. Collin, P. Newman, R. A. Bell, Jr, R. H. Adrian, T. E. |
spellingShingle |
Li, X. Roginsky, A. B. Ding, X.‐Z. Woodward, C. Collin, P. Newman, R. A. Bell, Jr, R. H. Adrian, T. E. Review of the Apoptosis Pathways in Pancreatic Cancer and the Anti‐apoptotic Effects of the Novel Sea Cucumber Compound, Frondoside A |
author_facet |
Li, X. Roginsky, A. B. Ding, X.‐Z. Woodward, C. Collin, P. Newman, R. A. Bell, Jr, R. H. Adrian, T. E. |
author_sort |
Li, X. |
title |
Review of the Apoptosis Pathways in Pancreatic Cancer and the Anti‐apoptotic Effects of the Novel Sea Cucumber Compound, Frondoside A |
title_short |
Review of the Apoptosis Pathways in Pancreatic Cancer and the Anti‐apoptotic Effects of the Novel Sea Cucumber Compound, Frondoside A |
title_full |
Review of the Apoptosis Pathways in Pancreatic Cancer and the Anti‐apoptotic Effects of the Novel Sea Cucumber Compound, Frondoside A |
title_fullStr |
Review of the Apoptosis Pathways in Pancreatic Cancer and the Anti‐apoptotic Effects of the Novel Sea Cucumber Compound, Frondoside A |
title_full_unstemmed |
Review of the Apoptosis Pathways in Pancreatic Cancer and the Anti‐apoptotic Effects of the Novel Sea Cucumber Compound, Frondoside A |
title_sort |
review of the apoptosis pathways in pancreatic cancer and the anti‐apoptotic effects of the novel sea cucumber compound, frondoside a |
publisher |
Wiley |
publishDate |
2008 |
url |
http://dx.doi.org/10.1196/annals.1414.025 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1196%2Fannals.1414.025 https://nyaspubs.onlinelibrary.wiley.com/doi/pdf/10.1196/annals.1414.025 |
genre |
Cucumaria frondosa |
genre_facet |
Cucumaria frondosa |
op_source |
Annals of the New York Academy of Sciences volume 1138, issue 1, page 181-198 ISSN 0077-8923 1749-6632 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1196/annals.1414.025 |
container_title |
Annals of the New York Academy of Sciences |
container_volume |
1138 |
container_issue |
1 |
container_start_page |
181 |
op_container_end_page |
198 |
_version_ |
1810440894654971904 |