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Abstract Title:

Piperlongumine inhibits head and neck squamous cell carcinoma proliferation by docking to Akt.

Abstract Source:

Phytother Res. 2020 Aug 15. Epub 2020 Aug 15. PMID: 32798277

Abstract Author(s):

Fei Lv, Mingming Deng, Jin Bai, Dan Zou, Jian Wang, Hong Li, Ye Zhang, Xu Ji

Article Affiliation:

Fei Lv

Abstract:

Piperlongumine (PL) is a biologically active alkaloid isolated from the long pepper roots and widely used as a traditional medicine in Ayurvedic medicine. However, the mechanism of PL's effect on head and neck squamous cell carcinoma (HNSCC) is not well understood. We performed cell experiments to confirm PL's inhibitory effect on HNSCC and employing cisplatin as positive control. Next, we conducted bioinformatics to predict PL's potential targets and verified by western blotting. Molecular docking, Biacore experiment and kinase activity assays were applied to elucidate the mechanism by which PL inhibited target activity. In vivo efficacy was verified by xenotransplantation and immunohistochemistry. PL inhibited proliferation, promoted late apoptosis, arrested cell cycle and inhibited DNA replication of the HEp-2 and FaDu cell lines. Employing bioinformatics, we found that PL's target was Akt and PL attenuated Akt phosphorylation. We found from molecular docking, Biacore experiment and kinase activity assay that PL inhibited Akt activation by docking to Akt to restrain its activity. In addition, PL significantly inhibited the growth of xenograft tumors by down regulating the expression of p-Akt in vivo. This study provides new insights into the molecular functions of PL and indicate its potential as a therapeutic agent for HNSCC.

Study Type : Animal Study, In Vitro Study

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Sayer Ji
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