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Depression: 21st Century Solutions + The Dark Side of Wheat

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Abstract Title:

Ginkgetin Blocks Constitutive STAT3 Activation and Induces Apoptosis through Induction of SHP-1 and PTEN Tyrosine Phosphatases.

Abstract Source:

Phytother Res. 2016 Apr ;30(4):567-76. Epub 2016 Jan 12. PMID: 27059688

Abstract Author(s):

Seung Ho Baek, Jae Hwi Lee, Jeong-Hyeon Ko, Hanwool Lee, Dongwoo Nam, Seok Geun Lee, Woong Mo Yang, Jae-Young Um, Junhee Lee, Sung-Hoon Kim, Bum Sang Shim, Kwang Seok Ahn

Article Affiliation:

Seung Ho Baek

Abstract:

Ginkgetin, a biflavone from Ginkgo biloba leaves, is known to exhibit antiinflammatory, antifungal, neuroprotective, and antitumor activities, but its precise mechanism of action has not been fully elucidated. Because the aberrant activation of STAT3 has been linked with regulation of inflammation, proliferation, invasion, and metastasis of tumors, we hypothesized that ginkgetin modulates the activation of STAT3 in tumor cells. We found that ginkgetin clearly suppressed constitutive phosphorylation of STAT3 through inhibition of the activation of upstream JAK1 and c-Src kinases and nuclear translocation of STAT3 on both A549 and FaDu cells. Treatment with sodium pervanadate reversed the ginkgetin-induced down-modulation of STAT3, thereby indicating a critical role for a PTP. We also found that ginkgetin strongly induced the expression of the SHP-1 and PTEN proteins and its mRNAs. Further, deletion of SHP-1 and PTEN genes by siRNA suppressed the induction of SHP-1 and PTEN, and reversed the inhibition of STAT3 activation. Ginkgetin induced apoptosis as characterized by an increased accumulation of cells in subG1 phase, positive Annexin V binding, loss of mitochondrial membrane potential, down-regulation of STAT3-regulated gene products, and cleavage of PARP. Overall, ginkgetin abrogates STAT3 signaling pathway through induction of SHP-1 and PTEN proteins, thus attenuating STAT3 phosphorylation and tumorigenesis.

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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