title: Two new isoquinoline alkaloids from Scolopendra subspinipes mutilans induce cell cycle arrest and apoptosis in human glioma cancer U87 cells.
abstract: Two new isoquinoline alkaloids 1-2 and seven known compounds 3-9 were isolated from the ethanol extract of centipede Scolopendra subspinipes mutilans L. Koch. The structures were elucidated by a combination of spectroscopic analyses including 1D and 2D NMR, and HRESIMS. Compounds 1-2 exhibited good cytotoxicity with IC50 values ranging from 1.19 to 31.28μM against six human cancer cell lines and low cytotoxicity against human normal liver L-02 cell lines, suggesting that compounds 1-2 had high specific cytotoxicity on human cancer cell lines. Further analyses showed that compounds 1-2 inhibited U87 cells proliferation by arresting cell cycle progress at G0/G1 phase and inducing apoptosis through loss of mitochondrial membrane potential (MMP), activation of caspase 9/3 and down-regulation of the Bcl-2/Bax protein ratio. The results suggest that compounds 1-2 induce apoptosis in U87 cells through the mitochondria apoptosis pathway, and they deserve further research as potential anti-glioma cancer agents.
authors.affiliation: The Engineering Research Centre of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ding
authors.affiliation: The Engineering Research Centre of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China.
authors.forename: Ya-Ru
authors.initials: YR
authors.lastname: Guo
authors.affiliation: The Engineering Research Centre of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China.
authors.forename: Rui-Ling
authors.initials: RL
authors.lastname: Wu
authors.affiliation: The Engineering Research Centre of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China. Electronic address: qiwy05@126.com.
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Qi
authors.affiliation: The Engineering Research Centre of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China; State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, Jiangsu 210009, PR China. Electronic address: 13913925346@126.com.
authors.forename: Han-Mei
authors.initials: HM
authors.lastname: Xu
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification; D017209:Apoptosis / Q000187:drug effects; D001181:Arthropods / Q000737:chemistry*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D005910:Glioma / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000737:chemistry* / Q000302:isolation & purification; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; C494826:BAX protein, human; C000595707:BCL2 protein, human; D007546:Isoquinolines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D020169:Caspases
keywords: Apoptosis; Cell cycle; Cytotoxicity; Isoquinoline alkaloid; Scolopendra subspinipes mutilans