Abstract
Despite recent advances in the treatment of chronic myelogenous leukemia (CML), the development of drug resistance and minimal residual disease remain major challenges for the treatment of CML patients, thus highlighting the need to develop innovative new approaches to improve therapeutic outcome. Myrtucommulone A (MCA) is a nonprenylated acylphloroglucinol isolated from the leaves of myrtle, a plant traditionally used in folk medicine. To date, studies addressing bioactivities of myrtle and its specific components are rare. Here, we investigated the biological effects of MCA, focusing on its anti-leukemic activity. As evidenced by fragmented nuclei after Hoechst/propidium iodide staining and poly (ADP-ribose) polymerase cleavage, MCA induces apoptosis in CML cells through down-regulation of anti-apoptotic proteins. Interestingly, we showed that chronic treatment with MCA at low doses induced senescence in CML cells. Taken together, this study highlights the chemotherapeutical potential of this natural product in human leukemia.
Keywords: Apoptosis, chronic myelogenous leukemia, mitochondrial pathway, myrtucommulone A, natural acylphloroglucinol, senescence.
Graphical Abstract
Anti-Cancer Agents in Medicinal Chemistry
Title:Dual Induction of Mitochondrial Apoptosis and Senescence in Chronic Myelogenous Leukemia by Myrtucommulone A
Volume: 15 Issue: 3
Author(s): Cindy Grandjenette, Michael Schnekenburger, Franck Morceau, Fabienne Mack, Katja Wiechmann, Oliver Werz, Mario Dicato and Marc Diederich
Affiliation:
Keywords: Apoptosis, chronic myelogenous leukemia, mitochondrial pathway, myrtucommulone A, natural acylphloroglucinol, senescence.
Abstract: Despite recent advances in the treatment of chronic myelogenous leukemia (CML), the development of drug resistance and minimal residual disease remain major challenges for the treatment of CML patients, thus highlighting the need to develop innovative new approaches to improve therapeutic outcome. Myrtucommulone A (MCA) is a nonprenylated acylphloroglucinol isolated from the leaves of myrtle, a plant traditionally used in folk medicine. To date, studies addressing bioactivities of myrtle and its specific components are rare. Here, we investigated the biological effects of MCA, focusing on its anti-leukemic activity. As evidenced by fragmented nuclei after Hoechst/propidium iodide staining and poly (ADP-ribose) polymerase cleavage, MCA induces apoptosis in CML cells through down-regulation of anti-apoptotic proteins. Interestingly, we showed that chronic treatment with MCA at low doses induced senescence in CML cells. Taken together, this study highlights the chemotherapeutical potential of this natural product in human leukemia.
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Grandjenette Cindy, Schnekenburger Michael, Morceau Franck, Mack Fabienne, Wiechmann Katja, Werz Oliver, Dicato Mario and Diederich Marc, Dual Induction of Mitochondrial Apoptosis and Senescence in Chronic Myelogenous Leukemia by Myrtucommulone A, Anti-Cancer Agents in Medicinal Chemistry 2015; 15 (3) . https://dx.doi.org/10.2174/1871520614666141202143757
DOI https://dx.doi.org/10.2174/1871520614666141202143757 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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