NDLI: Water-soluble oxoglaucine-Y(III), Dy(III) complexes: in vitro and in vivo anticancer activities by triggering DNA damage, leading to S phase arrest and apoptosis

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Water-soluble oxoglaucine-Y(III), Dy(III) complexes: in vitro and in vivo anticancer activities by triggering DNA damage, leading to S phase arrest and apoptosis

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Liang, Hong Qin, Jiao-lan Wei, Jian-hua Jiang, Yan-hua Shen, Wen-ying Li, Zhu-quan Chen, Zhen-feng Khan, Taj-malook Wang, Meng Liu, Yan-cheng
Description	Author Affiliation: Wei JH ( State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmacy, Guangxi Normal University, Guilin 541004, China. chenzf@gxnu.edu.cn hliang@gxnu.edu.cn.)
Abstract	Complexes of yttrium(III) and dysprosium(III) with the traditional Chinese medicine active ingredient oxoglaucine (OG), namely $[Y(OG)_{2}(NO_{3})_{3}]·CH_{3}OH$ (1) and $[Dy(OG)_{2}(NO_{3})_{3}]·H_{2}O$ (2), were synthesized and characterized by elemental analysis, IR, ESI-MS, $^{1}H$ and $^{13}C$ NMR as well as single-crystal X-ray diffraction analysis. In vitro the complexes exhibited higher anticancer activity than the free ligand OG against the tested cancer cell lines. Among the tested cell lines, HepG2 is the most sensitive to the complexes. Complex 2 can trigger DNA damage in HepG2 cells, resulting in cell cycle arrest in the S phase and leading to cell apoptosis. The S phase cell-cycle arrest is caused via the ATM (ataxia-telangiectasia mutated)-Chk2-Cdc25A pathway. Chk2 is phosphorylated and activated in an ATM-dependent manner. It, in turn, phosphorylates Cdc25A phosphatise on serine124, causing the inactivation of Cdc25A in ubiquitin-mediated proteolytic degradation. The cyclin-Cdk complexes of the S phase could also be inhibited by limited supply of cyclins A and E. This irreversible cell cycle arrest process ultimately induces mitochondria-involved apoptotic cell death via the activation of Bcl-2 protein. Complex 2 effectively inhibited tumour growth in the BEL-7402 xenograft mouse model and exhibited higher safety in vivo than cisplatin.
ISSN	14779226
Issue Number	25
Volume Number	44
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2015-07-07
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Antineoplastic Agents Apomorphine Analogs & Derivatives Coordination Complexes Dysprosium Topoisomerase Inhibitors Yttrium Animals Chemistry Pharmacology Therapeutic Use Apoptosis Drug Effects Cell Cycle Checkpoints Cell Line Cell Line, Tumor Cell Survival DNA Metabolism DNA Damage Humans Medicine, Chinese Traditional Mice Neoplasms Drug Therapy Pathology Proto-Oncogene Proteins C-bcl-2 S Phase Solubility Tumor Burden Water X-Ray Diffraction Journal Article Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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