title: Tetramethylpyrazine inhibits migration of SKOV3 human ovarian carcinoma cells and decreases the expression of interleukin-8 via the ERK1/2, p38 and AP-1 signaling pathways.
abstract: Interleukin-8 (IL-8) expression by melanoma cells may influence their metastatic capabilities. Tetramethylpyrazine (TMP) from Ligusticum wallichil Franch. possesses anti-inflammatory and antitumor activities. It has recently been suggested that autocrine IL-8 may play a role in tumor cell survival, invasion and migration. The role of TMP in association with IL-8 in the tumor cell migratory process remains unclear. The purpose of the present study was to determine whether TMP influences the migratory ability of a human ovarian carcinoma cell line (SKOV3) via regulation of IL-8 expression in vitro. Cell counts showed that treatment of SKOV3 with TMP (25-100 µg/ml) for 24 h did not decrease cell numbers, while an effect of TMP on the down-regulation of the expression of IL-8 was observed. In addition, migration of SKOV3 cells was suppressed after treatment with TMP (25-100 µg/ml) for 24 h. Therefore, expression of IL-8 by SKOV3 cells correlates with their metastatic potential. Western blot analysis revealed that ERK1/2 and p38 phosphorylation was blocked by TMP. Furthermore, IL-8 mRNA expression was inhibited significantly after co-incubation with PD98059 (ERK inhibitor) and SB203580 (p38 inhibitor), respectively. Notably, these changes were the results of activator protein-1 (AP-1) activity suppression rather than that of NF-κB. Our data suggest that TMP may inhibit tumor cell invasion and migration, at least in part, through its down-regulation of IL-8 expression. Our results provide evidence that anti-inflammation plays an important role in integrative cancer therapies.
authors.affiliation: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Chongqing Medical University, and Institute of Life Sciences, Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yin
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yang
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: He
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Chen
authors.forename: Hai-Zhong
authors.initials: HZ
authors.lastname: Liu
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Li
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Liu
authors.forename: Ying-Xiong
authors.initials: YX
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival; D018920:Coculture Techniques; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000473:pathology*; D010766:Phosphorylation; D011719:Pyrazines / Q000494:pharmacology*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; C508606:CXCL8 protein, human; D016209:Interleukin-8; D011719:Pyrazines; D018808:Transcription Factor AP-1; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; C017953:tetramethylpyrazine