Homoharringtonine-induced apoptosis of MDS cell line MUTZ-1 cells is mediated by the endoplasmic reticulum stress pathway.
Homoharringtonine has been shown to lead to apoptosis of leukemic cells in several studies. Here we showed that the endoplasmic reticulum (ER) may be the initial site of apoptotic signal induced by homoharringtonine in MUTZ-1 cells. After incubation with homoharringtonine, the percentage of apoptotic MUTZ-1 cells increased in a time-dependent manner, Ca(2+) translocated from ER pool to cytosol, the mitochondrial membrane potential decreased, and Bid protein translocated from ER to mitochondria. The activation of ER stress-associated proapoptotic factor CHOP and ER chaperones BiP and XBP1 genes followed by cleavage of caspase-3 but not caspase-4 protein were also observed.
Jie
Hu
H
Department of Hematology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Donghua
He
H
Xingkui
Xue
X
Liang
Gao
G
Wenjun
Wu
W
Xiaoyan
Han
H
Zhen
Cai
C
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006248:Harringtonines / Q000494:pharmacology*; D000077863:Homoharringtonine; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D006248:Harringtonines; D000077863:Homoharringtonine; D002118:Calcium