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

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.

• Authors: Qun Liu, Yong-Bo Peng, Ping Zhou, Lian-Wen Qi, Mu Zhang, Ning Gao, E-Hu Liu, Ping Li
• Journal: Molecular cancer (Mol Cancer) Vol. 12 Issue 1 Pg. 135 (Nov 12 2013) ISSN: 1476-4598 [Electronic] England
• PMID: 24215632 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Catechols
• Eukaryotic Initiation Factor-2
• shogaol
• CASP3 protein, human
• CASP7 protein, human
• Caspase 3
• Caspase 7

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Caspase 7 (metabolism)
• Catechols (chemistry, pharmacology)
• Enzyme Activation
• Eukaryotic Initiation Factor-2 (chemistry, metabolism)
• HL-60 Cells
• Humans
• Jurkat Cells
• Leukemia (drug therapy, enzymology, pathology)
• Leukocytes, Mononuclear (drug effects, physiology)
• Mice
• Mice, Inbred NOD
• Mice, Nude
• Mice, SCID
• Molecular Docking Simulation
• Phosphorylation
• Protein Processing, Post-Translational
• Proteolysis
• U937 Cells
• Xenograft Model Antitumor Assays