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A novel structural derivative of natural alkaloid ellipticine, MDPSQ, induces necrosis in leukemic cells

Shahabuddin, MS and Nambiar, Mridula and Moorthy, Balaji T and Naik, Prakruthi L and Choudhary, Bibha and Advirao, Gopal M and Raghavan, Sathees C (2011) A novel structural derivative of natural alkaloid ellipticine, MDPSQ, induces necrosis in leukemic cells. In: Investigational New Drugs, 29 (4). pp. 523-533.

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Abstract

DNA intercalating molecules are promising chemotherapeutic agents. In the present study, a novel DNA intercalating compound of pyrimido4',5':4,5]selenolo(2,3-b)quinoline series having 8-methyl-4-(3 diethylaminopropylamino) side chain is studied for its chemotherapeutic properties. Our results showed that 8-methyl-4-(3 diethylaminopropylamino) pyrimido 4',5':4,5] selenolo(2,3-b)quinoline (MDPSQ) induces cytotoxicity in a time- and concentration-dependent manner on leukemic cell lines. Both cell cycle analysis and tritiated thymidine assays revealed that MDPSQ affects DNA replication. Treatment with MDPSQ resulted in both elevated levels of DNA strand breaks and repair proteins, further indicating its cytotoxic effects. Besides, Annexin V/PI staining revealed that MDPSQ induces cell death by triggering necrosis rather than apoptosis.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Springer.
Keywords: Chemotherapy;Double-strand breaks;Cytotoxicity;DNA damage; Anti cancer drugs
Department/Centre: Division of Biological Sciences > Biochemistry
Depositing User: Id for Latest eprints
Date Deposited: 15 Jun 2011 05:42
Last Modified: 15 Jun 2011 05:42
URI: http://eprints.iisc.ac.in/id/eprint/38246

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