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A novel DNA intercalator, 8-methoxy pyrimido4 `,5 `:4,5]thieno (2,3-b)quinoline-4(3H)-one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor

Sharma, Sheetal and Panjamurthy, Kuppusamy and Choudhary, Bibha and Srivastava, Mrinal and Shahabuddin, MS and Giri, Ranjit and Advirao, Gopal M and Raghavan, Sathees C (2013) A novel DNA intercalator, 8-methoxy pyrimido4 `,5 `:4,5]thieno (2,3-b)quinoline-4(3H)-one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor. In: Molecular Carcinogenesis, 52 (6). pp. 413-425.

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Official URL: http://dx.doi.org/10.1002/mc.21867

Abstract

Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to John Wiley and Sons.
Keywords: Chemotherapy; DNA Intercalator; Double-Strand Breaks; Extrinsic Pathway of Apoptosis; DNA Damage; Anticancer Drug
Department/Centre: Division of Biological Sciences > Biochemistry
Depositing User: Francis Jayakanth
Date Deposited: 30 May 2013 11:05
Last Modified: 31 May 2013 05:36
URI: http://eprints.iisc.ac.in/id/eprint/46597

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