title: Tetramethypyrazine inhibits renal cell carcinoma cells through inhibition of NKG2D signaling pathways.
abstract: Tetramethypyrazine (TMP), one of the active compounds extracted from the traditional Chinese medicinal herb (Chuanxiong), has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms have not been fully elucidated. In the present study, the anticancer efficacy of TMP was investigated in human clear cell renal cell carcinoma (ccRCC) cells. We showed that TMP significantly inhibited ccRCC cell viability, proliferation, apoptosis, invasion and migration through the methods of MTT, flow cytometry, wound healing and transwell assays. Furthermore, reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunofluorescence results demonstrated TMP upregulation of the expression of NKG2D ligands (NKG2DLs) MHC class I chain-related molecules A and B (MICA/B) and epithelial cell expression marker of E-cadherin, and downregulation of mesenchymal cell expression markers of vimentin and fibronectin. Taken together, the inhibition of TMP on ccRCC cells might be mediated via inhibition of NKG2D related signaling pathway to further suppress epithelial-mesenchymal transition (EMT) progression. The binding of NKG2D to its ligands activates NK cells, giving the rationale for studies on the utilization of TMP as a potential cancer therapeutic compound to increase NK cells-mediated cytotoxicity against high MICA/B expression in cancer cells.
authors.affiliation: Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Luan
authors.affiliation: Clinical Molecular Biology Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Junli
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Hematology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xue
authors.affiliation: Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Kong
authors.affiliation: Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Central Research Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Clinical Molecular Biology Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Center of Evidence-Based Medicine, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Jia
mesh_terms: D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011719:Pyrazines; D014665:Vasodilator Agents; C017953:tetramethylpyrazine