A novel DNA intercalator, butylamino-pyrimido[4',5':4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells

Shahabuddin, MS and Nambiar, Mridula and Choudhary, Bibha and Advirao, Gopal M and Raghavan, Sathees C (2010) A novel DNA intercalator, butylamino-pyrimido[4',5':4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells. In: Investigational New Drugs, 28 (1). pp. 35-48.

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Abstract

DNA intercalators are one of the most commonly used chemotherapeutic agents. Novel intercalating compounds of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having a butylamino or piperazino group at fourth position (BPSQ and PPSQ, respectively) are studied. Our results showed that BPSQ induced cytotoxicity whereas PPSQ was cytostatic. The cytotoxicity induced by BPSQ was concentration- and time-dependent. Cell cycle analysis and tritiated thymidine assay revealed that BPSQ affects the cell cycle progression by arresting at S phase. The absence of p-histone H3 and reduction in the levels of PCNA in the cells treated with BPSQ further confirmed the cell cycle arrest. Further, annexin V staining, DNA fragmentation, nuclear condensation and changes in the expression levels of BCL2/BAD confirmed the activation of apoptosis. Activation of caspase 8 and lack of cleavage of caspase 9, caspase 3 and PARP suggest the possibility of BPSQ triggering extrinsic pathway for induction of apoptosis, which is discussed. Hence, we have identified a novel compound which would have clinical relevance in cancer chemotherapeutics.

Item Type:	Journal Article
Publication:	Investigational New Drugs
Publisher:	Springer
Additional Information:	Copyright for this article belongs to Springer.
Keywords:	Chemotherapy; Double-strand breaks; Cytotoxicity; DNA damage; Anticancer drug
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	27 Jan 2010 09:53
Last Modified:	19 Sep 2010 05:54
URI:	http://eprints.iisc.ac.in/id/eprint/25463

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