Homoharringtonine induces apoptosis and growth arrest in human myeloma cells.
Homoharringtonine (HHT) is a plant alkaloid with antileukemic activity which is currently being used for treatment of acute and chronic leukemias. The present studies have evaluated the effect of HHT on proliferation and apoptosis in human myeloma cells. Myeloma cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptotic cells and cell cycle were evaluated by flow cytometry. Level of caspase-8, caspase-9, caspase-3, and DNA repair enzyme poly (ADP-ribose) polymerase (PARP), were investigated using Western blot analysis. We found that HHT significantly inhibited the proliferation of human multiple myeloma (MM) cell lines and tumor cells from patients with relapsed refractory MM in a dose-dependent manner. HHT also induced apoptosis in myeloma cells as evidenced by flow cytometric detection of annexin V binding assay. This apoptotic process was associated with the activation of caspase-8, caspase-9, caspase-3 and PARP. The results also demonstrate that HHT potentiates dexamethasone-induced killing of MM cells. These findings indicate that HHT may be effective in the treatment of MM.
Lou
Yin-Jun
YJ
Department of Hematology, Institute of Hematology, The First Affiliated Hospital, ZheJiang University College of Medicine, Hangzhou, ZheJiang, China.
Qian
Wen-Bin
WB
Jin
Jie
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000032:analysis; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D006248:Harringtonines / Q000494:pharmacology*; D000077863:Homoharringtonine; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis
D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D000077863:Homoharringtonine; D003907:Dexamethasone; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases