期刊
MOLECULAR CANCER
卷 12, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1476-4598-12-135
关键词
6-shogaol; Leukemia; Apoptosis; Shotgun proteome; eIF2 alpha
资金
- National Science Foundation of China [81001618, 81202898]
- program for scientific innovation research of college graduate in Jiangsu province [CXZZ13_0328]
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 (eIF2 alpha), 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 eIF2 alpha at Ser51 of the N-terminal domain. Immunoblotting data indicated that 6-shogaol induced apoptosis through a process involving dephosphorylation of eIF2 alpha and caspase activation-dependent cleavage of eIF2 alpha. 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.
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