title: Omacetaxine mepesuccinate induces apoptosis and cell cycle arrest, promotes cell differentiation, and reduces telomerase activity in diffuse large B‑cell lymphoma cells.
abstract: Clinical studies have demonstrated that omacetaxine mepesuccinate exerts beneficial effects on acute myelogenous leukemia. It has been suggested that omacetaxine mepesuccinate, used alone or with interferon‑α or cytarabine, induces remission in patients with chronic myelogenous leukemia. These effects are possibly mediated by its ability to induce apoptosis of leukemia cells and inhibit the activity of telomerase. To determine whether omacetaxine mepesuccinate is beneficial in diffuse large B‑cell lymphoma (DLBCL), two DLBCL cell lines [a germinal center B cell‑like subtype (GCB) and an activated B cell‑like subtype (ABC)] were treated with omacetaxine mepesuccinate at various concentrations for different durations. The present study indicated that omacetaxine mepesuccinate exerts proapoptotic effects in the two cell types in a dose‑ and time‑dependent manner. The ABC subtype demonstrated increased sensitivity compared with the GCB subtype. At 40 ng/ml, omacetaxine mepesuccinate exhibited a marked proapoptotic effect on DLBCL cells compared with the other tumor cells investigated. Furthermore, omacetaxine mepesuccinate induced cell cycle arrest at G0/G1 phase, and promoted cell terminal differentiation of pro‑B cells. The present study also demonstrated that omacetaxine mepesuccinate exerted its antitumor effect by reducing telomerase activity. In conclusion, the present study demonstrated that omacetaxine mepesuccinate may induce apoptosis and cell cycle arrest, promote cell differentiation, and reduce telomerase activity in DLBCL cells, thus aiding the development of omacetaxine mepesuccinate‑based DLBCL therapeutic strategies.
authors.affiliation: Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Zhenzhu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zuo
authors.affiliation: Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Xinghu
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Yufu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wei
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D006248:Harringtonines / Q000494:pharmacology*; D000077863:Homoharringtonine; D006801:Humans; D016130:Immunophenotyping; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D000077863:Homoharringtonine; D019098:Telomerase