Dual Induction of Mitochondrial Apoptosis and Senescence in Chronic Myelogenous Leukemia by Myrtucommulone A
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.
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