title: Dual induction of mitochondrial apoptosis and senescence in chronic myelogenous leukemia by myrtucommulone A.
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.
authors.forename: Cindy
authors.initials: C
authors.lastname: Grandjenette
authors.forename: Michael
authors.initials: M
authors.lastname: Schnekenburger
authors.forename: Franck
authors.initials: F
authors.lastname: Morceau
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mack
authors.forename: Katja
authors.initials: K
authors.lastname: Wiechmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.forename: Mario
authors.initials: M
authors.lastname: Dicato
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Building 20 Room 303, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Korea. marcdiederich@snu.ac.kr.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects*; D015394:Molecular Structure; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; C455139:myrtucommulone A; D010696:Phloroglucinol