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Abstract Title:

Licochalcone C induced apoptosis in human oral squamous cell carcinoma cells by regulation of the JAK2/STAT3 signaling pathway.

Abstract Source:

J Cell Biochem. 2018 12 ;119(12):10118-10130. Epub 2018 Aug 20. PMID: 30129052

Abstract Author(s):

Ha-Na Oh, Ji-Hye Seo, Mee-Hyun Lee, Cheolhee Kim, Eunae Kim, Goo Yoon, Seung-Sik Cho, Young Sik Cho, Hyun Woo Choi, Jung-Hyun Shim, Jung-Il Chae

Article Affiliation:

Ha-Na Oh

Abstract:

Oral cancer is of an aggressive malignancy that arises on oral cavity and lip, 90% of cancers histologically originated in the squamous cells. Licochalcone (LC)C has been known as natural phenolic chalconoid substances, and its origin is the root of Glycyrrhiza glabra or Glycyrrhiza inflata. LCC inhibited oral squamous cell carcinoma (OSCC) cell viability, mitochondrial function, and anchorage-independent growth in a dose-dependent manner. To investigate the ability of LCC to target Janus kinase 2 (JAK2), we performed pull-down binding assay, kinase assay, and docking simulation. The molecular docking studies were performed between JAK2 and the potent inhibitor LCC. It was shown that LCC tightly interacted with ATP-binding site of JAK2. In addition, LCC inhibited the JAK2/signal transducer and activator of transcription 3 pathway, upregulated p21, and downregulated Bcl-2, Mcl-1, and Survivin, while it disrupted mitochondrial membrane potential and subsequently caused cytochrome c release with activation of multi-caspase, eventually leading to apoptosis in HN22 and HSC4 cells. LCC elevated the protein levels of Bax, cleaved Bid and PARP, and increased Apaf-1, and this effect was reversed by LCC treatment. Our results demonstrated that treatment of OSCC cells with LCC induced the death receptor (DR)4 and DR5 expression level with the generation of reactive oxygen species and the upregulation of CHOP protein expression. Taken together, these results could provide the basis for clinical application as a new therapeutic strategy in the treatment of oral cancer.

Study Type : In Vitro Study

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