title: Matrine activates PTEN to induce growth inhibition and apoptosis in V600EBRAF harboring melanoma cells.
abstract: Here, we report a natural chemical Matrine, which exhibits anti-melanoma potential with its PTEN activation mechanism. Matrine effectively inhibited proliferation of several carcinoma cell lines, including melanoma V600EBRAF harboring M21 cells. Flow cytometry analysis showed Matrine induced G0/G1 cell cycle arrest in M21 cells dose-dependently. Apoptosis in M21 cells induced by Matrine was identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis and Annexin-V/FITC staining. Molecular mechanistic study suggested that Matrine upregulated both mRNA level and protein expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN), leading to inhibition of the PI3K/Akt pathway. Downregulation of phosphor-Aktser473 by Matrine activated p21 and Bax, which contributed to G0/G1 cell cycle and apoptosis. Besides, Matrine enhanced the PI3K/Akt inhibition effects to inhibit the cell proliferation with PI3K inhibitor, LY2940002. In summary, our findings suggest Matrine is a promising antitumor drug candidate with its possible PTEN activation mechanisms for treating cancer diseases, such as melanomas.
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. joycejinhui@tongji.edu.cn
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Shuiying
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000871:Anthelmintics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D011807:Quinolizines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000871:Anthelmintics; D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011807:Quinolizines; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3; D000093842:Matrines
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