☆ 4.6 Article

Cytotoxic activity, DNA damage, cellular uptake, apoptosis and western blot analysis of ruthenium(II) polypyridyl complex against human lung decarcinoma A549 cell

JOURNAL OF INORGANIC BIOCHEMISTRY (2015)

期刊

JOURNAL OF INORGANIC BIOCHEMISTRY

卷 152, 期 -, 页码 1-9

出版社

ELSEVIER SCIENCE INC

DOI: 10.1016/j.jinorgbio.2015.08.012

关键词

Ruthenium(II) complex; Apoptosis; Cell cycle arrest; Mitochondrial membrane potential; Western blot analysis

类别

Biochemistry & Molecular Biology Chemistry, Inorganic & Nuclear

资金

High-Level Personnel Project of Guangdong Province
Joint Nature Science Fund of the Department of Science and Technology
Guangdong Pharmaceutical University [GYFYLH201315]

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Protocol

Reagent

摘要

A new ruthenium(II) Polypyridyl complex [Ru(dmp)(2)(PddPPn)](ClO4)(2) Ru1 was synthesized and characterized. The cytotoxic activity in vitro of the complex was evaluated by MTT method. Ru1 shows high effect on the inhibition of the cell growth against BEL-7402, HeLa, MG-63 and A549 cells with low IC50 values of 1.6 +/- 0.4, 9.0 +/- 0.8, 1.5 +/- 0.2 and 1.5 +/- 0.3 mu M, respectively. The cellular uptake indicates that Ru1 can enter into the cytoplasm and accumulate in the cell nuclei. Ru1 can induce apoptosis in A549 cells and enhance the levels of reactive oxygen species (ROS) and induce the decrease of mitochondrial membrane potential. In addition, Ru1 can downregulate the levels of Bcl-2, Bcl-x, Bak, and Bim expression and up-regulate the expression of Bag-1 and Bad. The complex induces apoptosis of A549 cells through an intrinsic ROS-mediated mitochondrial dysfunction pathway, which was accompanied by regulating the expression of caspases and Bcl-2 family proteins. (C) 2015 Elsevier Inc. All rights reserved.

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