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Mol Cancer. 2013 Nov 12;12(1):135. doi: 10.1186/1476-4598-12-135.

6-Shogaol induces apoptosis in human leukemia cells through a process involving caspase-mediated cleavage of eIF2α.

Author information

1
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. gaoning59@yahoo.com.cn.

Abstract

BACKGROUND:

6-Shogaol is a promising antitumor agent isolated from dietary ginger (Zingiber officinale). However, little is known about the efficacy of 6-shogaol on leukemia cells. Here we investigated the underlying mechanism of 6-shogaol induced apoptosis in human leukemia cells in vitro and in vivo.

METHODS:

Three leukemia cell lines and primary leukemia cells were used to investigate the apoptosis effect of 6-shogaol. A shotgun approach based on label-free proteome with LC-CHIP Q-TOF MS/MS was employed to identify the cellular targets of 6-shogaol and the differentially expressed proteins were analyzed by bioinformatics protocols.

RESULTS:

The present study indicated that 6-shogaol selectively induced apoptosis in transformed and primary leukemia cells but not in normal cells. Eukaryotic translation initiation factor 2 alpha (eIF2α), a key regulator in apoptosis signaling pathway, was significantly affected in both Jurkat and U937 proteome profiles. The docking results suggested that 6-shogaol might bind well to eIF2α at Ser51 of the N-terminal domain. Immunoblotting data indicated that 6-shogaol induced apoptosis through a process involving dephosphorylation of eIF2α and caspase activation-dependent cleavage of eIF2α. Furthermore, 6-shogaol markedly inhibited tumor growth and induced apoptosis in U937 xenograft mouse model.

CONCLUSION:

The potent anti-leukemia activity of 6-shogaol found both in vitro and in vivo in our study make this compound a potential anti-tumor agent for hematologic malignancies.

PMID:
24215632
PMCID:
PMC4176122
DOI:
10.1186/1476-4598-12-135
[Indexed for MEDLINE]
Free PMC Article

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