title: Analgesic-antitumor peptide inhibits proliferation and migration of SHG-44 human malignant glioma cells.
abstract: Malignant gliomas, the most common subtype of primary brain tumors, are characterized by high proliferation, great invasion, and neurological destruction and considered to be the deadliest of human cancers. Analgesic-antitumor peptide (AGAP), one of scorpion toxic polypeptides, has been shown to have antitumor activity. Here, we show that recombinant AGAP (rAGAP) not only inhibits the proliferation of gliomas cell SHG-44 and rat glioma cell C6, but also suppresses the migration of SHG-44 cells during wound healing. To explain these phenomena, we find that rAGAP leads to cell cycle of SHG-44 arrested in G1 phase accompanied by suppressing G1 cell cycle regulatory proteins CDK2, CDK6, and p-RB by means of the down-regulated protein expression of p-AKT. Meanwhile, rAGAP significantly decreases the production of NF-κB, BCL-2, p-p38, p-c-Jun, and p-Erk1/2 and further suppresses the activation of VEGF and MMP-9 in SHG-44 cells. These findings suggest rAGAP inhibit proliferation and migration of SHG-44 cells by arresting cell cycle and interfering p-AKT, NF-κB, BCL-2, and MAPK signaling pathways.
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, Life Sciences College, Nanjing Normal University, Nanjing 210097, Jiangsu, China.
authors.forename: Youlong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xueting
authors.initials: X
authors.lastname: Cai
authors.forename: Tingmei
authors.initials: T
authors.lastname: Ye
authors.forename: Jiege
authors.initials: J
authors.lastname: Huo
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Shuangquan
authors.initials: S
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D057075:Enzyme Assays; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005910:Glioma; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012604:Scorpion Venoms / Q000494:pharmacology*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D012604:Scorpion Venoms; D015222:Sodium Channels; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C477804:antitumor-analgesic peptide, Buthus martensii; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; D020782:Matrix Metalloproteinases