NDLI: NSK-01105 inhibits proliferation and induces apoptosis of prostate cancer cells by blocking the Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yu, Pengfei Ye, Liang Wang, Hongbo Du, Guangying Zhang, Jianzhao Zhang, Jinghai Tian, Jingwei
Description	Country affiliation: China Author Affiliation: Yu P ( School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China.)
Abstract	The purposes of this study are to investigate the antitumor activities of NSK-01105, a novel sorafenib derivative, in in vitro and in vivo models, and explore the potential mechanisms. The effects of NSK-01105 on proliferation and apoptosis of prostate cancer cells were established by cytotoxicity assays, apoptosis analysis, flow cytometry analysis, and Western blot analysis. Two xenograft tumor models were used to verify the therapeutic effect of NSK-01105 in vivo. NSK-01105 exhibited broad-spectrum antitumor activity, particularly in prostate cancer cells. Characterization of apoptosis morphology was observed, and the percentage of apoptosis-positive cells significantly increased after NSK-01105 treatment for 24 h. Furthermore, a significant increase of the 'sub-G1' population in LNCaP and PC-3 cells after NSK-01105 treatment was determined by cell cycle analysis. Tumor growth was significantly suppressed by once daily oral 30 mg/kg dose of NSK-01105 with the inhibition rates of 63.82% in LNCaP models and 64.29% in PC-3 models, respectively. The activation of Raf-1 kinase and epidermal growth factor receptor was downregulated by NSK-01105 at 10 µmol/L. Consequently, the dual inhibitions of Raf/MEK/ERK and PI3K/Akt/mTOR signal pathways were observed by Western blot analysis. Collectively, our results suggest a role of NSK-01105 in treatment for human prostate tumors by inhibiting cell proliferation and inducing apoptosis. NSK-01105 appears to be a promising orally active anticancer drug and deserves further investigation.
File Format	HTM / HTML
ISSN	10104283
Issue Number	3
Volume Number	36
e-ISSN	14230380
Journal	Tumor Biology
Language	English
Publisher	Springer
Publisher Date	2015-03-01
Publisher Place	Netherlands
Access Restriction	Subscribed
Subject Keyword	Discipline Medicine__semicolon__oncology Antineoplastic Agents Pharmacology Apoptosis Drug Effects Cell Proliferation Niacinamide Analogs & Derivatives Phenylurea Compounds Prostatic Neoplasms Drug Therapy Quinazolines Signal Transduction Cell Cycle Cell Line, Tumor Drug Resistance, Neoplasm Extracellular Signal-regulated Map Kinases Metabolism Hct116 Cells Ht29 Cells Hep G2 Cells Humans Map Kinase Kinase Kinases Mcf-7 Cells Male Phosphatidylinositol 3-kinases Proto-oncogene Proteins C-akt Proto-oncogene Proteins C-raf Tor Serine-threonine Kinases Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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