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DNA intercalative 4-butylaminopyrimido4',5':4,5]thieno(2,3-b)quinoline induces cell cycle arrest and apoptosis in leukemia cells

RohitKumar, Heggodu G and Asha, Kittur R and Raghavan, Sathees C and Rao, Gopal Advi M (2015) DNA intercalative 4-butylaminopyrimido4',5':4,5]thieno(2,3-b)quinoline induces cell cycle arrest and apoptosis in leukemia cells. In: CANCER CHEMOTHERAPY AND PHARMACOLOGY, 75 (6). pp. 1121-1133.

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Official URL: http://dx.doi.org/ 10.1007/s00280-015-2735-6


DNA intercalators are one of the interesting groups in cancer chemotherapy. The development of novel anticancer small molecule has gained remarkable interest over the last decade. In this study, we synthesized and investigated the ability of a tetracyclic-condensed quinoline compound, 4-butylaminopyrimido4',5':4,5]thieno(2,3-b)quinoline (BPTQ), to interact with double-stranded DNA and inhibit cancer cell proliferation. Circular dichroism, topological studies, molecular docking, absorbance, and fluorescence spectral titrations were employed to study the interaction of BPTQ with DNA. Cytotoxicity was studied by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. Further, cell cycle analysis by flow cytometry, annexin V staining, mitochondrial membrane potential assay, DNA fragmentation, and western blot analysis were used to elucidate the mechanism of action of BPTQ at the cellular level. Spectral, topological, and docking studies confirmed that BPTQ is a typical intercalator of DNA. BPTQ induces dose-dependent inhibitory effect on the proliferation of cancer cells by arresting cells at S and G2/M phase. Further, BPTQ activates the mitochondria-mediated apoptosis pathway, as explicated by a decrease in mitochondrial membrane potential, increase in the Bax:Bcl-2 ratio, and activation of caspases. These results confirmed that BPTQ is a DNA intercalative anticancer molecule, which could aid in the development of future cancer therapeutic agents.

Item Type: Journal Article
Publisher: SPRINGER
Additional Information: Copyright for this article belongs to the SPRINGER, 233 SPRING ST, NEW YORK, NY 10013 USA
Keywords: DNA intercalators; Chemotherapy; Apoptosis; Leukemia
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 22 Jun 2015 05:07
Last Modified: 22 Jun 2015 05:07
URI: http://eprints.iisc.ac.in/id/eprint/51718

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