NDLI: LG308, a Novel Synthetic Compound with Antimicrotubule Activity in Prostate Cancer Cells, Exerts Effective Antitumor Activity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Qin, Min Peng, Shihong Liu, Ning Hu, Meichun He, Yundong Li, Guoliang Chen, Huang He, Yuan Chen, Ang Wang, Xin Liu, Mingyao Chen, Yihua Yi, Zhengfang
Description	Author Affiliation: Qin M ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Peng S ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Liu N ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Hu M ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); He Y ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Li G ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Chen H ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); He Y ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Chen A ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Wang X ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Liu M ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Chen Y ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.)); Yi Z ( Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China (M.Q., S.P., N.L., M.H., Y.H., G.L., H.C., Y.H., A.C., X.W., M.L., Y.C., Z.Y.))
Abstract	Microtubule plays many different essential roles in the process of tumorigenesis in many eukaryotes, and targeting mitotic progression by disturbing microtubule dynamics is used as a common strategy for cancer treatment. Microtubule-targeted drugs, including paclitaxel and Vinca alkaloids, were previously considered to work primarily by increasing or decreasing the cellular microtubule mass. The tubulin/microtubule system, which is an integral component of the cytoskeleton, is a therapeutic target for prostate cancer. In this study, we found a novel synthetic compound, 8-fluoro-N-phenylacetyl-1, 3, 4, 9-tetrahydro-ß-carboline (LG308), which disrupted the microtubule organization via inhibiting the polymerization of microtubule in PC-3M and LNCaP prostate cancer cell lines. Further study proved that LG308 induced mitotic phase arrest and inhibited G2/M progression significantly in LNCaP and PC-3M cell lines in a dose-dependent manner, and these were associated with the upregulation of cyclin B1 and mitotic marker MPM-2 and the dephosphorylation of cdc2. Besides, the cell proliferation and colony formation of PC-3M and LNCaP cells were effectively inhibited by LG308. Furthermore, LG308 induced apoptosis and cell death in PC-3M and LNCaP cell lines in vitro. In vivo, LG308 dramatically suppressed the growth and metastasis of prostate cancer in both xenograft and orthotopic models. All these data indicate that LG308 is a promising anticancer candidate with antimitotic activity for the treatment of prostate cancer.
File Format	HTM / HTML
ISSN	00223565
Issue Number	3
Volume Number	355
e-ISSN	15210103
Journal	Journal of Pharmacology and Experimental Therapeutics
Language	English
Publisher	American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2015-12-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Research Support, Non-u.s. Gov't Cell Proliferation Tubulin Modulators Mitosis Humans Male Biosynthesis Discipline Pharmacology Cyclin B1 Journal Article Prostatic Neoplasms Cell Division Dose-response Relationship, Drug G2 Phase Cdc2 Protein Kinase Tumor Stem Cell Assay Drug Therapy Antineoplastic Agents Pharmacology Metabolism Drug Effects Xenograft Model Antitumor Assays Mitotic Index Pathology Animals Discipline Therapeutics Mice, Nude Microtubules Cell Line, Tumor Mice Pharmacokinetics Forkhead Transcription Factors Apoptosis
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Pharmacology

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