Induction of apoptosis in human leukemia cells by grape seed extract occurs via activation of c-Jun NH2-terminal kinase.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Ning GaoXianglin Shi

Abstract

To characterize the functional role of c-Jun NH(2)-terminal kinase (JNK) and other apoptotic pathways in grape seed extract (GSE)-induced apoptosis in human leukemia cells by using pharmacologic and genetic approaches. Jurkat cells were treated with various concentrations of GSE for 12 and 24 h or with 50 microg/mL GSE for various time intervals, after which apoptosis, caspase activation, and cell signaling pathways were evaluated. Parallel studies were done in U937 and HL-60 human leukemia cells. Exposure of Jurkat cells to GSE resulted in dose- and time-dependent increase in apoptosis and caspase activation, events associated with the pronounced increase in Cip1/p21 protein level. Furthermore, treatment of Jurkat cells with GSE resulted in marked increase in levels of phospho-JNK. Conversely, interruption of the JNK pathway by pharmacologic inhibitor (e.g., SP600125) or genetic (e.g., small interfering RNA) approaches displayed significant protection against GSE-mediated lethality in Jurkat cells. The result of the present study showed that GSE induces apoptosis in Jurkat cells through a process that involves sustained JNK activation and Cip1/p21 up-regulation, culminating in caspase activation.

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Citations

Dec 9, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Senping ChengXianglin Shi
Jul 31, 2009·The Journal of Nutrition·Manjinder KaurRajesh Agarwal
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Feb 27, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Fangzheng ChenSituo Zheng

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